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Driving Cancer Tumorigenesis and Metastasis Through UPR Signaling

  • Alexandra Papaioannou
  • Eric ChevetEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 414)

Abstract

In the tumor microenvironment, cancer cells encounter both external and internal factors that can lead to the accumulation of improperly folded proteins in the Endoplasmic Reticulum (ER) lumen, thus causing ER stress. When this happens, an adaptive mechanism named the Unfolded Protein Response (UPR) is triggered to help the cell cope with this change and restore protein homeostasis in the ER. Sequentially, one would expect that the activation of the three UPR branches, driven namely by IRE1, PERK, and ATF6, are crucial for the adaptation of cancer cells to the changing environment and thus for their survival and further propagation. Indeed, in the last few years, an increasing amount of studies has shown the implication of UPR signaling in different aspects of carcinogenesis and tumor progression. Features such as sustaining proliferation and resistance to cell death, genomic instability, altered metabolism, increased inflammation and tumor-immune infiltration, invasion and metastasis, and angiogenesis, defined as “the hallmarks of cancer”, can be regulated by the UPR machinery. At the same time, new potential therapeutic interventions applicable to different kinds of cancers are being revealed. In order to describe the emerging role of UPR in cancer biology, these are the points that will be discussed in this chapter.

List of Abbreviations

ADAM17

ADAM metallopeptidase domain 17

AKT

Protein kinase B (PKB)

ALL

Acute lymphoblastic leukemia

APC

Antigen-presenting cells

APY29

N2-1H-Benzimidazol-6-yl-N4-(5-cyclopropyl-1H-pyrazol-3-yl)-2,4-pyrimidinediamine

ASK1

Apoptosis signal-regulating kinase 1

ATF3

Activating transcription factor 3

ATF4

Activating transcription factor 4

ATF6

Activating transcription factor 6

ATF6f

ATF6 cytoplasmic domain

ATG5

Autophagy protein 5

ATM

Ataxia-telangiectasia mutated (Ser/Thr protein kinase)

BCR

Breakpoint cluster region

BiP

Binding immunoglobin protein or GRP78

CAC

Colitis-associated cancer

CAF

Cancer-associated fibroblasts

CCL2

Chemokine (C-C motif) ligand 2 or MCP-1

CD8/28/40/80/86

Cluster of differentiation 8/28/40/80/86

CHOP

C/EBP-homologous protein

CNS

Central nervous system

CreP

Protein phosphatase 1 regulatory subunit 15B (PPP1R15B)

CRT

Calreticulin

CXCL3/8/10/14

C-X-C motif chemokine ligand 3/8/10/14

DC

Dendritic cells

E2F

Family of transcription factors (TF) in higher eukaryotes

EC

Endothelial cells

ECM

Extracellular matrix

EGF

Epidermal growth factor

EGFR

Epidermal growth factor receptor

EGR-1

Early growth response protein 1

eIF2B

Guanine nucleotide exchange factor for the eukaryotic initiation factor 2

eIF2α

Eukaryotic initiation factor 2α

EMT

Epithelial-to-mesenchymal transition

EPR

Epiregulin

ER

Endoplasmic reticulum

ER+

Estrogen receptor positive

ErbB1

Synonym of EGFR

ERO1α

Endoplasmic reticulum oxidoreductase 1 alpha

FAK

Focal adhesion kinase

FGF

Fibroblast growth factor

FGF2

Fibroblast growth factor 2

FOXO

Forkhead box O

FOXP3

Forkhead box P3

GADD34

Growth arrest and DNA damage-inducible protein GADD34/Protein phosphatase 1 regulatory subunit 15A (PP1R15A)

GBM

Glioblastoma multiforme

GLUT1

Glucose transporter 1

gp96/GRP94

Glycoprotein 96/94 kDa glucose-regulated protein

GRP78

78 kDa glucose-regulated protein

HDAC

Histone deacetylase

HIF1α

Hypoxia-inducible factor 1-alpha

IL1/1β/2/6/8/10/17/23

Interleukin 1/1β/2/6/8/10/17/23

IRE1α

Endoribonuclease inositol-requiring enzyme 1 alpha

ISC

Intestinal stem cells

ISRIB

Integrated stress response inhibitor

JNK

c-Jun N-terminal kinase

Keap1

Kelch-like ECH-associated protein 1

KIRA

Kinase-inhibiting RNase attenuators

LAMP3

Lysosomal-associated membrane protein 3

LC3B

Microtubule-associated proteins 1A/1B-light chain 3B

MAF

MAF BZIP Transcription Factor

MAFB

MAF BZIP transcription factor B

MCP-1

Monocyte chemoattractant protein-1 or CCL2

MDSC

Myeloid-derived suppressor cells

MHC I/II

Major histocompatibility complex I/II

MIP-1α/MIP-1β

Macrophage inflammatory protein-1α/β

miRNA

Micro RNA

MMP

Matrix metalloproteinase

mRNA

Messenger RNA

mTOR

Mechanistic target of rapamycin

mTORC1

Mammalian target of rapamycin complex 1

ΜΦ

Macrophages

NFκB p65/RelA

Nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit

NRF2

Nuclear factor (erythroid-derived 2)-like 2

p53

Tumor protein p53

p97/VCP

Valosin-containing protein

PDI

Protein disulfide isomerase

PDIA5

Protein disulfide isomerase family A member 5

PERK

Protein kinase RNA-like endoplasmic reticulum kinase

PLCγ

Phospholipase C gamma

PP1c

Protein phosphatase 1 catalytic subunit

PTM

Post-translational modification

RhoA

Ras homolog gene family, member A

ROS

Reactive oxygen species

rRNA

Ribosomal RNA

RtcB

TRNA-splicing ligase RtcB homolog/C22orf28/HSPC117

RUVBL2

RuvB-like 2

S1P

Site-1 protease

S1PR1

Sphingosine-1-phosphate receptor 1

S2P

Site-2 protease

SCCA1

Squamous cell carcinoma antigen 1

SNAIL

Zinc finger protein SNAI1

SPARC

Secreted protein acidic and rich in cysteine

SRC

Tyrosine-protein kinase Src

STAT3/6

Signal transducer and activator of transcription-3/-6

TAC

Transit-amplifying cells

TAM

Tumor-associated macrophages

TDAG51

T-cell death-associated gene 51 protein

Tg

Thapsigargin

TGF-β

Transforming growth factor beta

TGF-β1

Transforming growth factor beta 1

THBS1

Thrombospondin 1

TNBC

Triple negative breast cancer

TNFα

Tumor necrosis factor alpha

TRAF2

TNF receptor-associated factor 2

Tun

Tunicamycin

Twist

Twist-related protein 1 (TWIST1)

UPR

Unfolded protein response

VEGF-A

Vascular endothelial growth factor A

VEGF

Vascular endothelial growth factor

VEGFR2

Vascular endothelial growth factor receptor 2

WNT

Wingless-related integration site

WNT11

WNT family member 11

XBP1

X-box binding protein 1

XBP1s

Spliced form (active) of X-box binding protein 1

Notes

Acknowledgements

This work was funded by grants from the Institut National du Cancer (INCa) and EU H2020 MSCA ITN-675448 (TRAINERS) to EC.

References

  1. Acosta-Alvear D, Zhou Y, Blais A, Tsikitis M, Lents NH, Arias C, Lennon CJ, Kluger Y, Dynlacht BD (2007) XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Mol Cell 27(1):53–66CrossRefGoogle Scholar
  2. Adachi Y, Yamamoto K, Okada T, Yoshida H, Harada A, Mori K (2008) ATF6 is a transcription factor specializing in the regulation of quality control proteins in the endoplasmic reticulum. Cell Struct Funct 33(1):75–89 JST.JSTAGE/csf/07044 [pii]CrossRefGoogle Scholar
  3. Adolph TE, Tomczak MF, Niederreiter L, Ko HJ, Bock J, Martinez-Naves E, Glickman JN, Tschurtschenthaler M, Hartwig J, Hosomi S, Flak MB, Cusick JL, Kohno K, Iwawaki T, Billmann-Born S, Raine T, Bharti R, Lucius R, Kweon MN, Marciniak SJ, Choi A, Hagen SJ, Schreiber S, Rosenstiel P, Kaser A, Blumberg RS (2014) Paneth cells as a site of origin for intestinal inflammation. Nature 503(7475):272–276. doi: 10.1038/nature12599 [pii]CrossRefGoogle Scholar
  4. Aguirre-Ghiso JA (2007) Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 7(11):834–846. doi: 10.1038/nrc2256CrossRefPubMedPubMedCentralGoogle Scholar
  5. Al-Rawashdeh FY, Scriven P, Cameron IC, Vergani PV, Wyld L (2010) Unfolded protein response activation contributes to chemoresistance in hepatocellular carcinoma. Eur J Gastroenterol Hepatol 22(9):1099–1105. doi: 10.1097/MEG.0b013e3283378405CrossRefPubMedGoogle Scholar
  6. Alam J, Stewart D, Touchard C, Boinapally S, Choi AM, Cook JL (1999) Nrf2, a Cap’n’Collar transcription factor, regulates induction of the heme oxygenase-1 gene. J Biol Chem 274(37):26071–26078CrossRefGoogle Scholar
  7. Alam J, Wicks C, Stewart D, Gong P, Touchard C, Otterbein S, Choi AM, Burow ME, Tou J (2000) Mechanism of heme oxygenase-1 gene activation by cadmium in MCF-7 mammary epithelial cells. Role of p38 kinase and Nrf2 transcription factor. J Biol Chem 275(36):27694–27702. doi: 10.1074/jbc.M004729200 [pii]
  8. Ali MM, Bagratuni T, Davenport EL, Nowak PR, Silva-Santisteban MC, Hardcastle A, McAndrews C, Rowlands MG, Morgan GJ, Aherne W, Collins I, Davies FE, Pearl LH (2011) Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response. EMBO J 30(5):894–905. doi: 10.1038/emboj.2011.18CrossRefPubMedPubMedCentralGoogle Scholar
  9. Allavena P, Mantovani A (2012) Immunology in the clinic review series; focus on cancer: tumour-associated macrophages: undisputed stars of the inflammatory tumour microenvironment. Clin Exp Immunol 167(2):195–205. doi: 10.1111/j.1365-2249.2011.04515.xCrossRefPubMedPubMedCentralGoogle Scholar
  10. Allavena P, Sica A, Garlanda C, Mantovani A (2008) The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol Rev 222:155–161. doi: 10.1111/j.1600-065X.2008.00607.xCrossRefPubMedGoogle Scholar
  11. Arai M, Kondoh N, Imazeki N, Hada A, Hatsuse K, Kimura F, Matsubara O, Mori K, Wakatsuki T, Yamamoto M (2006) Transformation-associated gene regulation by ATF6alpha during hepatocarcinogenesis. FEBS Lett 580(1):184–190. doi: 10.1016/j.febslet.2005.11.072 S0014-5793(05)01449-3 [pii]CrossRefPubMedGoogle Scholar
  12. Atkins C, Liu Q, Minthorn E, Zhang SY, Figueroa DJ, Moss K, Stanley TB, Sanders B, Goetz A, Gaul N, Choudhry AE, Alsaid H, Jucker BM, Axten JM, Kumar R (2013) Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res 73(6):1993–2002. doi: 10.1158/0008-5472.CAN-12-3109CrossRefPubMedGoogle Scholar
  13. Auf G, Jabouille A, Delugin M, Guerit S, Pineau R, North S, Platonova N, Maitre M, Favereaux A, Vajkoczy P, Seno M, Bikfalvi A, Minchenko D, Minchenko O, Moenner M (2013) High epiregulin expression in human U87 glioma cells relies on IRE1alpha and promotes autocrine growth through EGF receptor. BMC Cancer 13:597. doi: 10.1186/1471-2407-13-597 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  14. Auf G, Jabouille A, Guerit S, Pineau R, Delugin M, Bouchecareilh M, Magnin N, Favereaux A, Maitre M, Gaiser T, von Deimling A, Czabanka M, Vajkoczy P, Chevet E, Bikfalvi A, Moenner M (2010) Inositol-requiring enzyme 1alpha is a key regulator of angiogenesis and invasion in malignant glioma. Proc Natl Acad Sci USA 107(35):15553–15558. doi: 10.1073/pnas.0914072107CrossRefPubMedPubMedCentralGoogle Scholar
  15. Axten JM, Medina JR, Feng Y, Shu A, Romeril SP, Grant SW, Li WH, Heerding DA, Minthorn E, Mencken T, Atkins C, Liu Q, Rabindran S, Kumar R, Hong X, Goetz A, Stanley T, Taylor JD, Sigethy SD, Tomberlin GH, Hassell AM, Kahler KM, Shewchuk LM, Gampe RT (2012) Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-p yrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). J Med Chem 55(16):7193–7207. doi: 10.1021/jm300713sCrossRefPubMedGoogle Scholar
  16. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255):539–545. doi: 10.1016/S0140-6736(00)04046-0CrossRefPubMedGoogle Scholar
  17. Baum B, Settleman J, Quinlan MP (2008) Transitions between epithelial and mesenchymal states in development and disease. Semin Cell Dev Biol 19(3):294–308. doi: 10.1016/j.semcdb.2008.02.001 S1084-9521(08)00022-0 [pii]CrossRefPubMedGoogle Scholar
  18. Bertolotti A, Wang X, Novoa I, Jungreis R, Schlessinger K, Cho JH, West AB, Ron D (2001) Increased sensitivity to dextran sodium sulfate colitis in IRE1beta-deficient mice. J Clin Invest 107(5):585–593CrossRefGoogle Scholar
  19. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D (2000) Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2(6):326–332. doi: 10.1038/35014014CrossRefPubMedPubMedCentralGoogle Scholar
  20. Bi M, Naczki C, Koritzinsky M, Fels D, Blais J, Hu N, Harding H, Novoa I, Varia M, Raleigh J, Scheuner D, Kaufman RJ, Bell J, Ron D, Wouters BG, Koumenis C (2005) ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J 24(19):3470–3481. doi: 10.1038/sj.emboj.7600777 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  21. Binet F, Sapieha P (2015) ER stress and angiogenesis. Cell Metab 22(4):560–575. doi: 10.1016/j.cmet.2015.07.010CrossRefPubMedGoogle Scholar
  22. Bingle L, Brown NJ, Lewis CE (2002) The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 196(3):254–265. doi: 10.1002/path.1027CrossRefPubMedGoogle Scholar
  23. Blais JD, Addison CL, Edge R, Falls T, Zhao H, Wary K, Koumenis C, Harding HP, Ron D, Holcik M, Bell JC (2006) Perk-dependent translational regulation promotes tumor cell adaptation and angiogenesis in response to hypoxic stress. Mol Cell Biol 26(24):9517–9532. doi: 10.1128/MCB.01145-06 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  24. Blais JD, Filipenko V, Bi M, Harding HP, Ron D, Koumenis C, Wouters BG, Bell JC (2004) Activating transcription factor 4 is translationally regulated by hypoxic stress. Mol Cell Biol 24(17):7469–7482. doi: 10.1128/MCB.24.17.7469-7482.2004 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  25. Bobrovnikova-Marjon E, Grigoriadou C, Pytel D, Zhang F, Ye J, Koumenis C, Cavener D, Diehl JA (2010) PERK promotes cancer cell proliferation and tumor growth by limiting oxidative DNA damage. Oncogene 29(27):3881–3895. doi: 10.1038/onc.2010.153 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  26. Bouchecareilh M, Higa A, Fribourg S, Moenner M, Chevet E (2011) Peptides derived from the bifunctional kinase/RNase enzyme IRE1{alpha} modulate IRE1{alpha} activity and protect cells from endoplasmic reticulum stress. FASEB J 25(9):3115–3129. doi: 10.1096/fj.11-182931 [pii]CrossRefPubMedGoogle Scholar
  27. Boyault C, Gilquin B, Zhang Y, Rybin V, Garman E, Meyer-Klaucke W, Matthias P, Muller CW, Khochbin S (2006) HDAC6-p97/VCP controlled polyubiquitin chain turnover. EMBO J 25(14):3357–3366. doi: 10.1038/sj.emboj.7601210CrossRefPubMedPubMedCentralGoogle Scholar
  28. Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, Kaufman RJ, Ma D, Coen DM, Ron D, Yuan J (2005) A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science 307(5711):935–939. doi: 10.1126/science.1101902 307/5711/935 [pii]CrossRefPubMedGoogle Scholar
  29. Brewer JW, Diehl JA (2000) PERK mediates cell-cycle exit during the mammalian unfolded protein response. Proc Natl Acad Sci USA 97(23):12625–12630. doi: 10.1073/pnas.220247197 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  30. Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, Clark SG, Ron D (2002) IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415(6867):92–96. doi: 10.1038/415092a [pii]CrossRefGoogle Scholar
  31. Carlisle RE, Heffernan A, Brimble E, Liu L, Jerome D, Collins CA, Mohammed-Ali Z, Margetts PJ, Austin RC, Dickhout JG (2012) TDAG51 mediates epithelial-to-mesenchymal transition in human proximal tubular epithelium. Am J Physiol Renal Physiol 303(3):F467–481. doi: 10.1152/ajprenal.00481.2011 [pii]CrossRefPubMedGoogle Scholar
  32. Carrasco DR, Sukhdeo K, Protopopova M, Sinha R, Enos M, Carrasco DE, Zheng M, Mani M, Henderson J, Pinkus GS, Munshi N, Horner J, Ivanova EV, Protopopov A, Anderson KC, Tonon G, DePinho RA (2007) The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis. Cancer Cell 11(4):349–360CrossRefGoogle Scholar
  33. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2(5):401–404. doi: 10.1158/2159-8290.CD-12-0095CrossRefPubMedGoogle Scholar
  34. Chen L, Jarujaron S, Wu X, Sun L, Zha W, Liang G, Wang X, Gurley EC, Studer EJ, Hylemon PB, Pandak WM Jr, Zhang L, Wang G, Li X, Dent P, Zhou H (2009) HIV protease inhibitor lopinavir-induced TNF-alpha and IL-6 expression is coupled to the unfolded protein response and ERK signaling pathways in macrophages. Biochem Pharmacol 78(1):70–77. doi: 10.1016/j.bcp.2009.03.022CrossRefPubMedPubMedCentralGoogle Scholar
  35. Chen X, Iliopoulos D, Zhang Q, Tang Q, Greenblatt MB, Hatziapostolou M, Lim E, Tam WL, Ni M, Chen Y, Mai J, Shen H, Hu DZ, Adoro S, Hu B, Song M, Tan C, Landis MD, Ferrari M, Shin SJ, Brown M, Chang JC, Liu XS, Glimcher LH (2014) XBP1 promotes triple-negative breast cancer by controlling the HIF1alpha pathway. Nature 508(7494):103–107. doi: 10.1038/nature13119CrossRefPubMedPubMedCentralGoogle Scholar
  36. Chevet E, Hetz C, Samali A (2015) Endoplasmic reticulum stress-activated cell reprogramming in oncogenesis. Cancer Discov 5(6):586–597. doi: 10.1158/2159-8290.CD-14-1490CrossRefPubMedGoogle Scholar
  37. Cox JS, Walter P (1996) A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell 87(3):391–404CrossRefGoogle Scholar
  38. Cross BC, Bond PJ, Sadowski PG, Jha BK, Zak J, Goodman JM, Silverman RH, Neubert TA, Baxendale IR, Ron D, Harding HP (2012) The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proc Natl Acad Sci USA 109(15):E869–878. doi: 10.1073/pnas.1115623109CrossRefPubMedPubMedCentralGoogle Scholar
  39. Cubillos-Ruiz JR, Silberman PC, Rutkowski MR, Chopra S, Perales-Puchalt A, Song M, Zhang S, Bettigole SE, Gupta D, Holcomb K, Ellenson LH, Caputo T, Lee AH, Conejo-Garcia JR, Glimcher LH (2015) ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis. Cell 161(7):1527–1538. doi: 10.1016/j.cell.2015.05.025CrossRefPubMedPubMedCentralGoogle Scholar
  40. Cullinan SB, Diehl JA (2004) PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J Biol Chem 279(19):20108–20117CrossRefGoogle Scholar
  41. Cullinan SB, Zhang D, Hannink M, Arvisais E, Kaufman RJ, Diehl JA (2003) Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol Cell Biol 23(20):7198–7209CrossRefGoogle Scholar
  42. Dadey DY, Kapoor V, Khudanyan A, Urano F, Kim AH, Thotala D, Hallahan DE (2016) The ATF6 pathway of the ER stress response contributes to enhanced viability in glioblastoma. Oncotarget 7(2):2080–2092. doi: 10.18632/oncotarget.6712CrossRefPubMedGoogle Scholar
  43. Das I, Krzyzosiak A, Schneider K, Wrabetz L, D’Antonio M, Barry N, Sigurdardottir A, Bertolotti A (2015) Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. Science 348(6231):239–242. doi: 10.1126/science.aaa4484CrossRefPubMedPubMedCentralGoogle Scholar
  44. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7(1):11–20. doi: 10.1016/j.cmet.2007.10.002 S1550-4131(07)00295-1 [pii]CrossRefPubMedGoogle Scholar
  45. Dejeans N, Pluquet O, Lhomond S, Grise F, Bouchecareilh M, Juin A, Meynard-Cadars M, Bidaud-Meynard A, Gentil C, Moreau V, Saltel F, Chevet E (2012) Autocrine control of glioma cells adhesion and migration through IRE1alpha-mediated cleavage of SPARC mRNA. J Cell Sci 125(Pt 18):4278–4287. doi: 10.1242/jcs.099291CrossRefPubMedGoogle Scholar
  46. Del Vecchio CA, Feng Y, Sokol ES, Tillman EJ, Sanduja S, Reinhardt F, Gupta PB (2014) De-differentiation confers multidrug resistance via noncanonical PERK-Nrf2 signaling. PLoS Biol 12(9):e1001945. doi: 10.1371/journal.pbio.1001945 PBIOLOGY-D-14-00485 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  47. Deng Y, Wang ZV, Tao C, Gao N, Holland WL, Ferdous A, Repa JJ, Liang G, Ye J, Lehrman MA, Hill JA, Horton JD, Scherer PE (2013) The Xbp1s/GalE axis links ER stress to postprandial hepatic metabolism. J Clin Invest 123(1):455–468. doi: 10.1172/JCI62819 [pii]CrossRefPubMedGoogle Scholar
  48. Denoyelle C, Abou-Rjaily G, Bezrookove V, Verhaegen M, Johnson TM, Fullen DR, Pointer JN, Gruber SB, Su LD, Nikiforov MA, Kaufman RJ, Bastian BC, Soengas MS (2006) Anti-oncogenic role of the endoplasmic reticulum differentially activated by mutations in the MAPK pathway. Nat Cell Biol 8(10):1053–1063. doi: 10.1038/ncb1471 [pii]CrossRefPubMedGoogle Scholar
  49. Dicks N, Gutierrez K, Michalak M, Bordignon V, Agellon LB (2015) Endoplasmic reticulum stress, genome damage, and cancer. Front Oncol 5:11. doi: 10.3389/fonc.2015.00011CrossRefPubMedPubMedCentralGoogle Scholar
  50. Dioufa N, Chatzistamou I, Farmaki E, Papavassiliou AG, Kiaris H (2009) p53 antagonizes the unfolded protein response and inhibits ground glass hepatocyte development during endoplasmic reticulum stress. Exp Biol Med (Maywood) 237(10):1173–1180. doi: 10.1258/ebm.2012.012140 [pii]CrossRefGoogle Scholar
  51. Dioufa N, Chatzistamou I, Farmaki E, Papavassiliou AG, Kiaris H (2012) p53 antagonizes the unfolded protein response and inhibits ground glass hepatocyte development during endoplasmic reticulum stress. Exp Biol Med (Maywood) 237(10):1173–1180. doi: 10.1258/ebm.2012.012140CrossRefGoogle Scholar
  52. Drogat B, Auguste P, Nguyen DT, Bouchecareilh M, Pineau R, Nalbantoglu J, Kaufman RJ, Chevet E, Bikfalvi A, Moenner M (2007) IRE1 signaling is essential for ischemia-induced vascular endothelial growth factor-A expression and contributes to angiogenesis and tumor growth in vivo. Cancer Res 67(14):6700–6707. doi: 10.1158/0008-5472.CAN-06-3235 67/14/6700 [pii]CrossRefPubMedGoogle Scholar
  53. Duplan E, Giaime E, Viotti J, Sevalle J, Corti O, Brice A, Ariga H, Qi L, Checler F, Alves da Costa C (2013) ER-stress-associated functional link between Parkin and DJ-1 via a transcriptional cascade involving the tumor suppressor p53 and the spliced X-box binding protein XBP-1. J Cell Sci 126(Pt 9):2124–2133. doi: 10.1242/jcs.127340 [pii]CrossRefPubMedGoogle Scholar
  54. Epple LM, Dodd RD, Merz AL, Dechkovskaia AM, Herring M, Winston BA, Lencioni AM, Russell RL, Madsen H, Nega M, Dusto NL, White J, Bigner DD, Nicchitta CV, Serkova NJ, Graner MW (2013) Induction of the unfolded protein response drives enhanced metabolism and chemoresistance in glioma cells. PLoS ONE 8(8):e73267. doi: 10.1371/journal.pone.0073267 PONE-D-12-22337 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  55. Farooqi AA, Li K-T, Fayyaz S, Chang Y-T, Ismail M, Liaw C-C, Yuan S-SF, Tang J-Y, Chang H-W (2015) Anticancer drugs for the modulation of endoplasmic reticulum stress and oxidative stress. Tumor Biology 36(8):5743–5752. doi: 10.1007/s13277-015-3797-0CrossRefPubMedPubMedCentralGoogle Scholar
  56. Feng R, Zhai WL, Yang HY, Jin H, Zhang QX (2011) Induction of ER stress protects gastric cancer cells against apoptosis induced by cisplatin and doxorubicin through activation of p38 MAPK. Biochem Biophys Res Commun 406(2):299–304. doi: 10.1016/j.bbrc.2011.02.036 S0006-291X(11)00219-1 [pii]CrossRefPubMedGoogle Scholar
  57. Feng YX, Sokol ES, Del Vecchio CA, Sanduja S, Claessen JH, Proia TA, Jin DX, Reinhardt F, Ploegh HL, Wang Q, Gupta PB (2014) Epithelial-to-mesenchymal transition activates PERK-eIF2alpha and sensitizes cells to endoplasmic reticulum stress. Cancer Discov 4(6):702–715. doi: 10.1158/2159-8290.CD-13-0945 [pii]CrossRefPubMedGoogle Scholar
  58. Forbes SA, Tang G, Bindal N, Bamford S, Dawson E, Cole C, Kok CY, Jia M, Ewing R, Menzies A, Teague JW, Stratton MR, Futreal PA (2009) COSMIC (the catalogue of somatic mutations in cancer): a resource to investigate acquired mutations in human cancer. Nucleic Acids Res 38(Database issue):D652–657. doi:  10.1093/nar/gkp995 [pii]
  59. Fox RM, Hanlon CD, Andrew DJ (2010) The CrebA/Creb3-like transcription factors are major and direct regulators of secretory capacity. J Cell Biol 191(3):479–492. doi: 10.1083/jcb.201004062 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  60. Futamura Y, Tashiro E, Hironiwa N, Kohno J, Nishio M, Shindo K, Imoto M (2007) Trierixin, a novel Inhibitor of ER stress-induced XBP1 activation from Streptomyces sp. II. structure elucidation. J Antibiot (Tokyo) 60(9):582–585. doi: 10.1038/ja.2007.74 JST.JSTAGE/antibiotics/60.582 [pii]CrossRefGoogle Scholar
  61. Galdiero MR, Garlanda C, Jaillon S, Marone G, Mantovani A (2013) Tumor associated macrophages and neutrophils in tumor progression. J Cell Physiol 228(7):1404–1412. doi: 10.1002/jcp.24260CrossRefPubMedGoogle Scholar
  62. Gallagher CM, Garri C, Cain EL, Ang KK, Wilson CG, Chen S, Hearn BR, Jaishankar P, Aranda-Diaz A, Arkin MR, Renslo AR, Walter P (2016) Ceapins are a new class of unfolded protein response inhibitors, selectively targeting the ATF6alpha branch. Elife 5. doi: 10.7554/eLife.11878
  63. Gallagher CM, Walter P (2016) Ceapins inhibit ATF6alpha signaling by selectively preventing transport of ATF6alpha to the Golgi apparatus during ER stress. Elife 5. doi: 10.7554/eLife.11880
  64. Ghosh R, Wang L, Wang ES, Perera BG, Igbaria A, Morita S, Prado K, Thamsen M, Caswell D, Macias H, Weiberth KF, Gliedt MJ, Alavi MV, Hari SB, Mitra AK, Bhhatarai B, Schurer SC, Snapp EL, Gould DB, German MS, Backes BJ, Maly DJ, Oakes SA, Papa FR (2014a) Allosteric inhibition of the IRE1alpha RNase preserves cell viability and function during endoplasmic reticulum stress. Cell. doi: 10.1016/j.cell.2014.07.002 S0092-8674(14)00878-2 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  65. Ghosh R, Wang L, Wang ES, Perera BG, Igbaria A, Morita S, Prado K, Thamsen M, Caswell D, Macias H, Weiberth KF, Gliedt MJ, Alavi MV, Hari SB, Mitra AK, Bhhatarai B, Schurer SC, Snapp EL, Gould DB, German MS, Backes BJ, Maly DJ, Oakes SA, Papa FR (2014b) Allosteric inhibition of the IRE1alpha RNase preserves cell viability and function during endoplasmic reticulum stress. Cell 158(3):534–548. doi: 10.1016/j.cell.2014.07.002CrossRefPubMedPubMedCentralGoogle Scholar
  66. Ginos MA, Page GP, Michalowicz BS, Patel KJ, Volker SE, Pambuccian SE, Ondrey FG, Adams GL, Gaffney PM (2004) Identification of a gene expression signature associated with recurrent disease in squamous cell carcinoma of the head and neck. Cancer Res 64(1):55–63CrossRefGoogle Scholar
  67. Gomez BP, Riggins RB, Shajahan AN, Klimach U, Wang A, Crawford AC, Zhu Y, Zwart A, Wang M, Clarke R (2007) Human X-box binding protein-1 confers both estrogen independence and antiestrogen resistance in breast cancer cell lines. FASEB J 21(14):4013–4027. doi: 10.1096/fj.06-7990com [pii]CrossRefPubMedGoogle Scholar
  68. Gonzalez-Perez A, Perez-Llamas C, Deu-Pons J, Tamborero D, Schroeder MP, Jene-Sanz A, Santos A, Lopez-Bigas N (2013) IntOGen-mutations identifies cancer drivers across tumor types. Nat Methods 10(11):1081–1082. doi: 10.1038/nmeth.2642CrossRefPubMedPubMedCentralGoogle Scholar
  69. Goodall JC, Wu C, Zhang Y, McNeill L, Ellis L, Saudek V, Gaston JS (2010) Endoplasmic reticulum stress-induced transcription factor, CHOP, is crucial for dendritic cell IL-23 expression. Proc Natl Acad Sci USA 107(41):17698–17703. doi: 10.1073/pnas.1011736107CrossRefPubMedPubMedCentralGoogle Scholar
  70. Granados DP, Tanguay PL, Hardy MP, Caron E, de Verteuil D, Meloche S, Perreault C (2009) ER stress affects processing of MHC class I-associated peptides. BMC Immunol 10:10. doi: 10.1186/1471-2172-10-10CrossRefPubMedPubMedCentralGoogle Scholar
  71. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O’Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR (2007) Patterns of somatic mutation in human cancer genomes. Nature 446(7132):153–158. doi: 10.1038/nature05610 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  72. Grohmann U, Fallarino F, Puccetti P (2003) Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol 24(5):242–248CrossRefGoogle Scholar
  73. Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, Calderaro J, Bioulac-Sage P, Letexier M, Degos F, Clement B, Balabaud C, Chevet E, Laurent A, Couchy G, Letouze E, Calvo F, Zucman-Rossi J (2012) Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet 44(6):694–698. doi: 10.1038/ng.2256 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  74. Halliday M, Radford H, Zents KAM, Molloy C, Moreno JA, Verity NC, Smith E, Ortori CA, Barrett DA, Bushell M, Mallucci GR (2017) Repurposed drugs targeting eIF2alpha-P-mediated translational repression prevent neurodegeneration in mice. Brain. doi: 10.1093/brain/awx074CrossRefPubMedPubMedCentralGoogle Scholar
  75. Hambardzumyan D, Gutmann DH, Kettenmann H (2016) The role of microglia and macrophages in glioma maintenance and progression. Nat Neurosci 19(1):20–27. doi: 10.1038/nn.4185CrossRefPubMedPubMedCentralGoogle Scholar
  76. Harding HP, Zhang Y, Ron D (1999) Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397(6716):271–274. doi: 10.1038/16729CrossRefPubMedPubMedCentralGoogle Scholar
  77. Haze K, Yoshida H, Yanagi H, Yura T, Mori K (1999) Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell 10(11):3787–3799CrossRefGoogle Scholar
  78. He L, Kim SO, Kwon O, Jeong SJ, Kim MS, Lee HG, Osada H, Jung M, Ahn JS, Kim BY (2009) ATM blocks tunicamycin-induced endoplasmic reticulum stress. FEBS Lett 583(5):903–908. doi: 10.1016/j.febslet.2009.02.002 S0014-5793(09)00094-5 [pii]CrossRefPubMedGoogle Scholar
  79. Heijmans J, de Jeude JFVL, Koo BK, Rosekrans SL, Wielenga MC, van de Wetering M, Ferrante M, Lee AS, Onderwater JJ, Paton JC, Paton AW, Mommaas AM, Kodach LL, Hardwick JC, Hommes DW, Clevers H, Muncan V, van den Brink GR (2013) ER stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response. Cell Rep 3(4):1128–1139CrossRefGoogle Scholar
  80. Henry KA, Blank HM, Hoose SA, Polymenis M (2010) The unfolded protein response is not necessary for the G1/S transition, but it is required for chromosome maintenance in Saccharomyces cerevisiae. PLoS ONE 5(9):e12732. doi: 10.1371/journal.pone.0012732CrossRefPubMedPubMedCentralGoogle Scholar
  81. Hetz C, Chevet E, Harding HP (2013) Targeting the unfolded protein response in disease. Nat Rev Drug Discov 12(9):703–719. doi: 10.1038/nrd3976 [pii]CrossRefPubMedGoogle Scholar
  82. Hetz C, Thielen P, Matus S, Nassif M, Court F, Kiffin R, Martinez G, Cuervo AM, Brown RH, Glimcher LH (2009) XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev 23(19):2294–2306CrossRefGoogle Scholar
  83. Higa A, Taouji S, Lhomond S, Jensen D, Fernandez-Zapico ME, Simpson JC, Pasquet JM, Schekman R, Chevet E (2014) Endoplasmic reticulum stress-activated transcription factor ATF6alpha requires the disulfide isomerase PDIA5 to modulate chemoresistance. Mol Cell Biol 34(10):1839–1849. doi: 10.1128/MCB.01484-13 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  84. Hollien J, Lin JH, Li H, Stevens N, Walter P, Weissman JS (2009) Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J Cell Biol 186(3):323–331CrossRefGoogle Scholar
  85. Hollien J, Weissman JS (2006) Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science 313(5783):104–107CrossRefGoogle Scholar
  86. Hsu JL, Chiang PC, Guh JH (2009) Tunicamycin induces resistance to camptothecin and etoposide in human hepatocellular carcinoma cells: role of cell-cycle arrest and GRP78. Naunyn Schmiedebergs Arch Pharmacol 380(5):373–382. doi: 10.1007/s00210-009-0453-5CrossRefPubMedGoogle Scholar
  87. Hu R, Warri A, Jin L, Zwart A, Riggins RB, Clarke R (2014) NFkappaB signaling is required for XBP1 (U and S) mediated effects on antiestrogen responsiveness and cell fate decisions in breast cancer. Mol Cell Biol. doi: 10.1128/MCB.00847-14 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  88. Huber AL, Lebeau J, Guillaumot P, Petrilli V, Malek M, Chilloux J, Fauvet F, Payen L, Kfoury A, Renno T, Chevet E, Manie SN (2013) p58(IPK)-mediated attenuation of the proapoptotic PERK-CHOP pathway allows malignant progression upon low glucose. Mol Cell 49(6):1049–1059CrossRefGoogle Scholar
  89. Hussain SF, Yang D, Suki D, Aldape K, Grimm E, Heimberger AB (2006) The role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses. Neuro Oncol 8(3):261–279. doi: 10.1215/15228517-2006-008CrossRefPubMedPubMedCentralGoogle Scholar
  90. Iwakoshi NN, Pypaert M, Glimcher LH (2007) The transcription factor XBP-1 is essential for the development and survival of dendritic cells. J Exp Med 204(10):2267–2275. doi: 10.1084/jem.20070525CrossRefPubMedPubMedCentralGoogle Scholar
  91. Iwawaki T, Hosoda A, Okuda T, Kamigori Y, Nomura-Furuwatari C, Kimata Y, Tsuru A, Kohno K (2001) Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress. Nat Cell Biol 3:158–164. doi: 10.1038/35055065CrossRefGoogle Scholar
  92. Jain RK (2003) Molecular regulation of vessel maturation. Nat Med 9(6):685–693. doi: 10.1038/nm0603-685CrossRefPubMedGoogle Scholar
  93. Jamison S, Lin Y, Lin W (2015) Pancreatic endoplasmic reticulum kinase activation promotes medulloblastoma cell migration and invasion through induction of vascular endothelial growth factor A. PLoS ONE 10(3):e0120252. doi: 10.1371/journal.pone.0120252CrossRefPubMedPubMedCentralGoogle Scholar
  94. Jurkin J, Henkel T, Nielsen AF, Minnich M, Popow J, Kaufmann T, Heindl K, Hoffmann T, Busslinger M, Martinez J (2014) The mammalian tRNA ligase complex mediates splicing of XBP1 mRNA and controls antibody secretion in plasma cells. EMBO J. doi: 10.15252/embj.201490332 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  95. Karali E, Bellou S, Stellas D, Klinakis A, Murphy C, Fotsis T (2014) VEGF signals through ATF6 and PERK to promote endothelial cell survival and angiogenesis in the absence of ER stress. Mol Cell 54(4):559–572. doi: 10.1016/j.molcel.2014.03.022CrossRefPubMedPubMedCentralGoogle Scholar
  96. Kaser A, Lee A-H, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EES, Higgins DE, Schreiber S, Glimcher LH, Blumberg RS (2008) XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134(5):743–756. doi: 10.1016/j.cell.2008.07.021CrossRefPubMedPubMedCentralGoogle Scholar
  97. Kawamura T, Tashiro E, Yamamoto K, Shindo K, Imoto M (2008) SAR study of a novel triene-ansamycin group compound, quinotrierixin, and related compounds, as inhibitors of ER stress-induced XBP1 activation. J Antibiot (Tokyo) 61(5):303–311. doi: 10.1038/ja.2008.43 JST.JSTAGE/antibiotics/61.303 [pii]CrossRefGoogle Scholar
  98. Kharabi Masouleh B, Geng H, Hurtz C, Chan LN, Logan AC, Chang MS, Huang C, Swaminathan S, Sun H, Paietta E, Melnick AM, Koeffler P, Muschen M (2014) Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia. Proc Natl Acad Sci USA 111(21):E2219–2228. doi: 10.1073/pnas.1400958111 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  99. Kirk SJ, Cliff JM, Thomas JA, Ward TH (2009) Biogenesis of secretory organelles during B cell differentiation. J Leukoc Biol 87(2):245–255. doi: 10.1189/jlb.1208774 [pii]CrossRefPubMedGoogle Scholar
  100. Komohara Y, Ohnishi K, Kuratsu J, Takeya M (2008) Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas. J Pathol 216(1):15–24. doi: 10.1002/path.2370CrossRefPubMedGoogle Scholar
  101. Kosmaczewski SG, Edwards TJ, Han SM, Eckwahl MJ, Meyer BI, Peach S, Hesselberth JR, Wolin SL, Hammarlund M (2014) The RtcB RNA ligase is an essential component of the metazoan unfolded protein response. EMBO Rep. doi: 10.15252/embr.201439531 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  102. Kozutsumi Y, Segal M, Normington K, Gething MJ, Sambrook J (1988) The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature 332(6163):462–464. doi: 10.1038/332462a0CrossRefPubMedGoogle Scholar
  103. Lee AH, Iwakoshi NN, Anderson KC, Glimcher LH (2003) Proteasome inhibitors disrupt the unfolded protein response in myeloma cells. Proc Natl Acad Sci USA 100(17):9946–9951CrossRefGoogle Scholar
  104. Lee K, Tirasophon W, Shen X, Michalak M, Prywes R, Okada T, Yoshida H, Mori K, Kaufman RJ (2002) IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev 16(4):452–466CrossRefGoogle Scholar
  105. Lerner AG, Upton JP, Praveen PV, Ghosh R, Nakagawa Y, Igbaria A, Shen S, Nguyen V, Backes BJ, Heiman M, Heintz N, Greengard P, Hui S, Tang Q, Trusina A, Oakes SA, Papa FR (2012) IRE1alpha induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab 16(2):250–264. doi: 10.1016/j.cmet.2012.07.007 S1550-4131(12)00284-7. [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  106. Lhomond S, Pallares N, Barroso K, Schmit K, Dejeans N, Fazli H, Taouji S, Patterson JB, Chevet E (2015) Adaptation of the secretory pathway in cancer through IRE1 signaling. Methods Mol Biol 1292:177–194. doi: 10.1007/978-1-4939-2522-3_13CrossRefPubMedGoogle Scholar
  107. Li H, Chen X, Gao Y, Wu J, Zeng F, Song F (2014) XBP1 induces snail expression to promote epithelial-to-mesenchymal transition and invasion of breast cancer cells. Cell Signal. doi: 10.1016/j.cellsig.2014.09.018 S0898-6568(14)00322-2 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  108. Lin YH, Friederichs J, Black MA, Mages J, Rosenberg R, Guilford PJ, Phillips V, Thompson-Fawcett M, Kasabov N, Toro T, Merrie AE, van Rij A, Yoon HS, McCall JL, Siewert JR, Holzmann B, Reeve AE (2007) Multiple gene expression classifiers from different array platforms predict poor prognosis of colorectal cancer. Clin Cancer Res Official J Am Assoc Cancer Res 13(2 Pt 1):498–507. doi: 10.1158/1078-0432.CCR-05-2734CrossRefGoogle Scholar
  109. Lu Y, Liang FX, Wang X (2014) A synthetic biology approach identifies the mammalian UPR RNA ligase RtcB. Mol Cell 55(5):758–770. doi: 10.1016/j.molcel.2014.06.032 S1097-2765(14)00566-8 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  110. Ma Y, Hendershot LM (2004) The role of the unfolded protein response in tumour development: friend or foe? Nat Rev Cancer 4(12):966–977. doi: 10.1038/nrc1505 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  111. Mahadevan NR, Anufreichik V, Rodvold JJ, Chiu KT, Sepulveda H, Zanetti M (2012) Cell-extrinsic effects of tumor ER stress imprint myeloid dendritic cells and impair CD8+ T cell priming. PLoS ONE 7(12):e51845. doi: 10.1371/journal.pone.0051845CrossRefPubMedPubMedCentralGoogle Scholar
  112. Mahadevan NR, Rodvold J, Sepulveda H, Rossi S, Drew AF, Zanetti M (2011) Transmission of endoplasmic reticulum stress and pro-inflammation from tumor cells to myeloid cells. Proc Natl Acad Sci USA 108(16):6561–6566CrossRefGoogle Scholar
  113. Maines MD (1988) Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2(10):2557–2568CrossRefGoogle Scholar
  114. Mantovani A, Sozzani S, Locati M, Allavena P, Sica A (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23(11):549–555CrossRefGoogle Scholar
  115. Mardones P, Martinez G, Hetz C (2015) Control of systemic proteostasis by the nervous system. Trends Cell Biol 25(1):1–10. doi: 10.1016/j.tcb.2014.08.001CrossRefPubMedGoogle Scholar
  116. Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, Chiavarina B, Pavlides S, Wang C, Whitaker-Menezes D, Daumer KM, Lin Z, Witkiewicz AK, Flomenberg N, Howell A, Pestell RG, Knudsen ES, Sotgia F, Lisanti MP (2010) Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: a new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells. Cell Cycle 9(16):3256–3276. doi: 10.4161/cc.9.16.12553CrossRefPubMedPubMedCentralGoogle Scholar
  117. Martino MB, Jones L, Brighton B, Ehre C, Abdulah L, Davis CW, Ron D, O’Neal WK, Ribeiro CM (2013) The ER stress transducer IRE1beta is required for airway epithelial mucin production. Mucosal Immunol 6(3):639–654. doi: 10.1038/mi.2012.105CrossRefGoogle Scholar
  118. Martinon F, Chen X, Lee A-H, Glimcher LH (2010a) TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nat Immunol 11(5):411–418. doi: 10.1038/ni.1857CrossRefPubMedPubMedCentralGoogle Scholar
  119. Martinon F, Chen X, Lee AH, Glimcher LH (2010b) TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nat Immunol 11(5):411–418CrossRefGoogle Scholar
  120. Marza E, Taouji S, Barroso K, Raymond AA, Guignard L, Bonneu M, Pallares-Lupon N, Dupuy JW, Fernandez-Zapico ME, Rosenbaum J, Palladino F, Dupuy D, Chevet E (2015) Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription. EMBO Rep 16(3):332–340. doi: 10.15252/embr.201439123CrossRefPubMedPubMedCentralGoogle Scholar
  121. Maurel M, Chevet E, Tavernier J, Gerlo S (2014) Getting RIDD of RNA: IRE1 in cell fate regulation. Trends Biochem Sci 39(5):245–254. doi: 10.1016/j.tibs.2014.02.008 S0968-0004(14)00033-4 [pii]CrossRefPubMedGoogle Scholar
  122. Mimura N, Fulciniti M, Gorgun G, Tai YT, Cirstea D, Santo L, Hu Y, Fabre C, Minami J, Ohguchi H, Kiziltepe T, Ikeda H, Kawano Y, French M, Blumenthal M, Tam V, Kertesz NL, Malyankar UM, Hokenson M, Pham T, Zeng Q, Patterson JB, Richardson PG, Munshi NC, Anderson KC (2012) Blockade of XBP1 splicing by inhibition of IRE1alpha is a promising therapeutic option in multiple myeloma. Blood 119(24):5772–5781. doi: 10.1182/blood-2011-07-366633CrossRefPubMedPubMedCentralGoogle Scholar
  123. Morales C, Rachidi S, Hong F, Sun S, Ouyang X, Wallace C, Zhang Y, Garret-Mayer E, Wu J, Liu B, Li Z (2014) Immune chaperone gp96 drives the contributions of macrophages to inflammatory colon tumorigenesis. Cancer Res 74(2):446–459. doi: 10.1158/0008-5472.CAN-13-1677CrossRefPubMedGoogle Scholar
  124. Mori K, Ma W, Gething MJ, Sambrook J (1993) A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus. Cell 74(4):743–756 0092-8674(93)90521-Q [pii]CrossRefGoogle Scholar
  125. Mujcic H, Nagelkerke A, Rouschop KM, Chung S, Chaudary N, Span PN, Clarke B, Milosevic M, Sykes J, Hill RP, Koritzinsky M, Wouters BG (2013) Hypoxic activation of the PERK/eIF2alpha arm of the unfolded protein response promotes metastasis through induction of LAMP3. Clin Cancer Res 19(22):6126–6137. doi: 10.1158/1078-0432.CCR-13-0526CrossRefPubMedGoogle Scholar
  126. Nagelkerke A, Bussink J, Mujcic H, Wouters BG, Lehmann S, Sweep FC, Span PN (2013) Hypoxia stimulates migration of breast cancer cells via the PERK/ATF4/LAMP3-arm of the unfolded protein response. Breast Cancer Res BCR 15(1):R2. doi: 10.1186/bcr3373CrossRefPubMedGoogle Scholar
  127. Nakajima S, Hiramatsu N, Hayakawa K, Saito Y, Kato H, Huang T, Yao J, Paton AW, Paton JC, Kitamura M (2011) Selective abrogation of BiP/GRP78 blunts activation of NF-kappaB through the ATF6 branch of the UPR: involvement of C/EBPbeta and mTOR-dependent dephosphorylation of Akt. Mol Cell Biol 31(8):1710–1718. doi: 10.1128/MCB.00939-10 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  128. Nguyen T, Nioi P, Pickett CB (2009) The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 284(20):13291–13295. doi: 10.1074/jbc.R900010200CrossRefPubMedPubMedCentralGoogle Scholar
  129. Niederreiter L, Fritz TM, Adolph TE, Krismer AM, Offner FA, Tschurtschenthaler M, Flak MB, Hosomi S, Tomczak MF, Kaneider NC, Sarcevic E, Kempster SL, Raine T, Esser D, Rosenstiel P, Kohno K, Iwawaki T, Tilg H, Blumberg RS, Kaser A (2013) ER stress transcription factor Xbp1 suppresses intestinal tumorigenesis and directs intestinal stem cells. J Exp Med 210(10):2041–2056. doi: 10.1084/jem.20122341 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  130. Nieto MA, Cano A (2012) The epithelial-mesenchymal transition under control: global programs to regulate epithelial plasticity. Semin Cancer Biol 22(5–6):361–368. doi: 10.1016/j.semcancer.2012.05.003 S1044-579X(12)00079-X [pii]CrossRefPubMedGoogle Scholar
  131. Norian LA, Rodriguez PC, O’Mara LA, Zabaleta J, Ochoa AC, Cella M, Allen PM (2009) Tumor-infiltrating regulatory dendritic cells inhibit CD8+ T cell function via L-arginine metabolism. Cancer Res 69(7):3086–3094. doi: 10.1158/0008-5472.CAN-08-2826CrossRefPubMedPubMedCentralGoogle Scholar
  132. Novoa I, Zeng H, Harding HP, Ron D (2001) Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J Cell Biol 153(5):1011–1022CrossRefGoogle Scholar
  133. Obacz J, Avril T, Le Reste PJ, Urra H, Quillien V, Hetz C, Chevet E (2017) Endoplasmic reticulum proteostasis in glioblastoma-From molecular mechanisms to therapeutic perspectives. Sci Signal 10(470). doi: 10.1126/scisignal.aal2323CrossRefPubMedGoogle Scholar
  134. Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, Shiosaka S, Hammarback JA, Urano F, Imaizumi K (2006) Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 26(24):9220–9231CrossRefGoogle Scholar
  135. Oromendia AB, Dodgson SE, Amon A (2012) Aneuploidy causes proteotoxic stress in yeast. Genes Dev 26(24):2696–2708. doi: 10.1101/gad.207407.112CrossRefPubMedPubMedCentralGoogle Scholar
  136. Osorio F, Tavernier SJ, Hoffmann E, Saeys Y, Martens L, Vetters J, Delrue I, De Rycke R, Parthoens E, Pouliot P, Iwawaki T, Janssens S, Lambrecht BN (2014) The unfolded-protein-response sensor IRE-1alpha regulates the function of CD8alpha+ dendritic cells. Nat Immunol 15(3):248–257. doi: 10.1038/ni.2808CrossRefPubMedGoogle Scholar
  137. Paez D, Labonte MJ, Bohanes P, Zhang W, Benhanim L, Ning Y, Wakatsuki T, Loupakis F, Lenz HJ (2012) Cancer dormancy: a model of early dissemination and late cancer recurrence. Clin Cancer Res Official J Am Assoc Cancer Res 18(3):645–653. doi: 10.1158/1078-0432.CCR-11-2186CrossRefGoogle Scholar
  138. Papandreou I, Denko NC, Olson M, Van Melckebeke H, Lust S, Tam A, Solow-Cordero DE, Bouley DM, Offner F, Niwa M, Koong AC (2011) Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. Blood 117(4):1311–1314. doi: 10.1182/blood-2010-08-303099 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  139. Park SH, Kim J, Do KH, Park J, Oh CG, Choi HJ, Song BG, Lee SJ, Kim YS, Moon Y (2014) Activating transcription factor 3-mediated chemo-intervention with cancer chemokines in a noncanonical pathway under endoplasmic reticulum stress. J Biol Chem 289(39):27118–27133. doi: 10.1074/jbc.M114.568717CrossRefPubMedPubMedCentralGoogle Scholar
  140. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321(5897):1807–1812. doi: 10.1126/science.1164382 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  141. Pereira ER, Liao N, Neale GA, Hendershot LM (2010) Transcriptional and post-transcriptional regulation of proangiogenic factors by the unfolded protein response. PLoS One 5(9). doi: 10.1371/journal.pone.0012521
  142. Plate L, Cooley CB, Chen JJ, Paxman RJ, Gallagher CM, Madoux F, Genereux JC, Dobbs W, Garza D, Spicer TP, Scampavia L, Brown SJ, Rosen H, Powers ET, Walter P, Hodder P, Wiseman RL, Kelly JW (2016) Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation. Elife 5. doi: 10.7554/eLife.15550
  143. Pluquet O, Dejeans N, Bouchecareilh M, Lhomond S, Pineau R, Higa A, Delugin M, Combe C, Loriot S, Cubel G, Dugot-Senant N, Vital A, Loiseau H, Gosline SJ, Taouji S, Hallett M, Sarkaria JN, Anderson K, Wu W, Rodriguez FJ, Rosenbaum J, Saltel F, Fernandez-Zapico ME, Chevet E (2013) Posttranscriptional regulation of PER1 underlies the oncogenic function of IREalpha. Cancer Res 73(15):4732–4743. doi: 10.1158/0008-5472.CAN-12-3989 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  144. Pollard JW (2004) Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 4(1):71–78. doi: 10.1038/nrc1256CrossRefPubMedGoogle Scholar
  145. Pytel D, Majsterek I, Diehl JA (2016) Tumor progression and the different faces of the PERK kinase. Oncogene 35(10):1207–1215. doi: 10.1038/onc.2015.178CrossRefPubMedGoogle Scholar
  146. Ramaswamy S, Tamayo P, Rifkin R, Mukherjee S, Yeang CH, Angelo M, Ladd C, Reich M, Latulippe E, Mesirov JP, Poggio T, Gerald W, Loda M, Lander ES, Golub TR (2001) Multiclass cancer diagnosis using tumor gene expression signatures. Proc Natl Acad Sci USA 98(26):15149–15154. doi: 10.1073/pnas.211566398CrossRefPubMedPubMedCentralGoogle Scholar
  147. Ranganathan AC, Zhang L, Adam AP, Aguirre-Ghiso JA (2006) Functional coupling of p38-induced up-regulation of BiP and activation of RNA-dependent protein kinase-like endoplasmic reticulum kinase to drug resistance of dormant carcinoma cells. Cancer Res 66(3):1702–1711. doi: 10.1158/0008-5472.CAN-05-3092CrossRefPubMedPubMedCentralGoogle Scholar
  148. Ray A, Zhang S, Rentas C, Caldwell KA, Caldwell GA (2014) RTCB-1 mediates neuroprotection via XBP-1 mRNA splicing in the unfolded protein response pathway. J Neurosci 34(48):16076–16085. doi: 10.1523/JNEUROSCI.1945-14.2014 34/48/16076 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  149. Ri M, Tashiro E, Oikawa D, Shinjo S, Tokuda M, Yokouchi Y, Narita T, Masaki A, Ito A, Ding J, Kusumoto S, Ishida T, Komatsu H, Shiotsu Y, Ueda R, Iwawaki T, Imoto M, Iida S (2012) Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing. Blood Cancer J 2(7):e79. doi: 10.1038/bcj.2012.26CrossRefPubMedPubMedCentralGoogle Scholar
  150. Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8(7):519–529CrossRefGoogle Scholar
  151. Rouschop KM, van den Beucken T, Dubois L, Niessen H, Bussink J, Savelkouls K, Keulers T, Mujcic H, Landuyt W, Voncken JW, Lambin P, van der Kogel AJ, Koritzinsky M, Wouters BG (2010) The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. J Clin Invest 120(1):127–141. doi: 10.1172/JCI40027 [pii]CrossRefPubMedGoogle Scholar
  152. Rzymski T, Milani M, Singleton DC, Harris AL (2009) Role of ATF4 in regulation of autophagy and resistance to drugs and hypoxia. Cell Cycle 8(23):3838–3847 10086 [pii]CrossRefGoogle Scholar
  153. Rzymski T, Petry A, Kracun D, Riess F, Pike L, Harris AL, Gorlach A (2012) The unfolded protein response controls induction and activation of ADAM17/TACE by severe hypoxia and ER stress. Oncogene 31(31):3621–3634. doi: 10.1038/onc.2011.522CrossRefPubMedGoogle Scholar
  154. Sanches M, Duffy NM, Talukdar M, Thevakumaran N, Chiovitti D, Canny MD, Lee K, Kurinov I, Uehling D, Al-awar R, Poda G, Prakesch M, Wilson B, Tam V, Schweitzer C, Toro A, Lucas JL, Vuga D, Lehmann L, Durocher D, Zeng Q, Patterson JB, Sicheri F (2014) Structure and mechanism of action of the hydroxy-aryl-aldehyde class of IRE1 endoribonuclease inhibitors. Nat Commun 5:4202. doi: 10.1038/ncomms5202CrossRefPubMedPubMedCentralGoogle Scholar
  155. Schewe DM, Aguirre-Ghiso JA (2008) ATF6alpha-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivo. Proc Natl Acad Sci USA 105(30):10519–10524. doi: 10.1073/pnas.0800939105 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  156. Sengupta S, Sharma CG, Jordan VC (2010) Estrogen regulation of X-box binding protein-1 and its role in estrogen induced growth of breast and endometrial cancer cells. Horm Mol Biol Clin Investig 2(2):235–243. doi: 10.1515/HMBCI.2010.025CrossRefPubMedPubMedCentralGoogle Scholar
  157. Shen J, Chen X, Hendershot L, Prywes R (2002) ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev Cell 3(1):99–111 S1534580702002034 [pii]CrossRefGoogle Scholar
  158. Shen J, Prywes R (2004) Dependence of site-2 protease cleavage of ATF6 on prior site-1 protease digestion is determined by the size of the luminal domain of ATF6. J Biol Chem 279(41):43046–43051. doi: 10.1074/jbc.M408466200 [pii]CrossRefPubMedGoogle Scholar
  159. Shen Q, Uray IP, Li Y, Krisko TI, Strecker TE, Kim HT, Brown PH (2008) The AP-1 transcription factor regulates breast cancer cell growth via cyclins and E2F factors. Oncogene 27(3):366–377. doi: 10.1038/sj.onc.1210643CrossRefPubMedGoogle Scholar
  160. Sheshadri N, Catanzaro JM, Bott A, Sun Y, Ullman E, Chen E, Pan JA, Wu S, Crawford HC, Zhang J, Zong WX (2014) SCCA1/SerpinB3 promotes oncogenesis and epithelial-mesenchymal transition via the unfolded protein response and IL-6 signaling. Cancer Res. doi: 10.1158/0008-5472.CAN-14-0798 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  161. Shi Y, Vattem KM, Sood R, An J, Liang J, Stramm L, Wek RC (1998) Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Mol Cell Biol 18(12):7499–7509CrossRefGoogle Scholar
  162. Shoulders MD, Ryno LM, Genereux JC, Moresco JJ, Tu PG, Wu C, Yates JR 3rd, Su AI, Kelly JW, Wiseman RL (2013) Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments. Cell Rep 3(4):1279–1292. doi: 10.1016/j.celrep.2013.03.024 S2211-1247(13)00131-9 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  163. Sidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR, Li H, Gamache K, Gallagher CM, Ang KK, Wilson C, Okreglak V, Ashkenazi A, Hann B, Nader K, Arkin MR, Renslo AR, Sonenberg N, Walter P (2013) Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife 2:e00498. doi: 10.7554/eLife.00498 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  164. Sidrauski C, McGeachy AM, Ingolia NT, Walter P (2015a) The small molecule ISRIB reverses the effects of eIF2alpha phosphorylation on translation and stress granule assembly. Elife 4. doi: 10.7554/eLife.05033
  165. Sidrauski C, Tsai JC, Kampmann M, Hearn BR, Vedantham P, Jaishankar P, Sokabe M, Mendez AS, Newton BW, Tang EL, Verschueren E, Johnson JR, Krogan NJ, Fraser CS, Weissman JS, Renslo AR, Walter P (2015b) Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response. Elife 4:e07314. doi: 10.7554/eLife.07314CrossRefPubMedPubMedCentralGoogle Scholar
  166. Tam AB, Koong AC, Niwa M (2014) Ire1 has distinct catalytic mechanisms for XBP1/HAC1 splicing and RIDD. Cell Reports 9:1–9CrossRefGoogle Scholar
  167. Tang CH, Ranatunga S, Kriss CL, Cubitt CL, Tao J, Pinilla-Ibarz JA, Del Valle JR, Hu CC (2014) Inhibition of ER stress-associated IRE-1/XBP-1 pathway reduces leukemic cell survival. J Clin Invest 124(6):2585–2598. doi: 10.1172/JCI73448 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  168. Tanjore H, Cheng DS, Degryse AL, Zoz DF, Abdolrasulnia R, Lawson WE, Blackwell TS (2011) Alveolar epithelial cells undergo epithelial-to-mesenchymal transition in response to endoplasmic reticulum stress. J Biol Chem 286(35):30972–30980. doi: 10.1074/jbc.M110.181164 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  169. Taylor RC, Dillin A (2013) XBP-1 is a cell-nonautonomous regulator of stress resistance and longevity. Cell 153(7):1435–1447. doi: 10.1016/j.cell.2013.05.042CrossRefPubMedPubMedCentralGoogle Scholar
  170. Thevenot PT, Sierra RA, Raber PL, Al-Khami AA, Trillo-Tinoco J, Zarreii P, Ochoa AC, Cui Y, Del Valle L, Rodriguez PC (2014) The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors. Immunity 41(3):389–401. doi: 10.1016/j.immuni.2014.08.015CrossRefPubMedPubMedCentralGoogle Scholar
  171. Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139(5):871–890. doi: 10.1016/j.cell.2009.11.007 S0092-8674(09)01419-6 [pii]CrossRefPubMedGoogle Scholar
  172. Ja Thorpe, Schwarze SR (2010) IRE1alpha controls cyclin A1 expression and promotes cell proliferation through XBP-1. Cell Stress Chaperones 15:497–508. doi: 10.1007/s12192-009-0163-4CrossRefGoogle Scholar
  173. Toledo CM, Ding Y, Hoellerbauer P, Davis RJ, Basom R, Girard EJ, Lee E, Corrin P, Hart T, Bolouri H, Davison J, Zhang Q, Hardcastle J, Aronow BJ, Plaisier CL, Baliga NS, Moffat J, Lin Q, Li XN, Nam DH, Lee J, Pollard SM, Zhu J, Delrow JJ, Clurman BE, Olson JM, Paddison PJ (2015) Genome-wide CRISPR-Cas9 screens reveal loss of redundancy between PKMYT1 and WEE1 in glioblastoma stem-like cells. Cell Rep 13(11):2425–2439. doi: 10.1016/j.celrep.2015.11.021CrossRefPubMedPubMedCentralGoogle Scholar
  174. Tsaytler P, Harding HP, Ron D, Bertolotti A (2011) Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science 332(6025):91–94. doi: 10.1126/science.1201396 [pii]CrossRefPubMedGoogle Scholar
  175. Tsuru A, Fujimoto N, Takahashi S, Saito M, Nakamura D, Iwano M, Iwawaki T, Kadokura H, Ron D, Kohno K (2013) Negative feedback by IRE1beta optimizes mucin production in goblet cells. Proc Natl Acad Sci USA 110(8):2864–2869CrossRefGoogle Scholar
  176. Ueno T, Toi M, Saji H, Muta M, Bando H, Kuroi K, Koike M, Inadera H, Matsushima K (2000) Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clin Cancer Res 6(8):3282–3289PubMedGoogle Scholar
  177. Ulianich L, Garbi C, Treglia AS, Punzi D, Miele C, Raciti GA, Beguinot F, Consiglio E, Di Jeso B (2008) ER stress is associated with dedifferentiation and an epithelial-to-mesenchymal transition-like phenotype in PC Cl3 thyroid cells. J Cell Sci 121(Pt 4):477–486. doi: 10.1242/jcs.017202 [pii]CrossRefPubMedGoogle Scholar
  178. Upton JP, Wang L, Han D, Wang ES, Huskey NE, Lim L, Truitt M, McManus MT, Ruggero D, Goga A, Papa FR, Oakes SA (2012) IRE1alpha cleaves select microRNAs during ER stress to derepress translation of proapoptotic Caspase-2. Science 338(6108):818–822. doi: 10.1126/science.1226191 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  179. Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP, Ron D (2000) Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287(5453):664–666 8218 [pii]CrossRefGoogle Scholar
  180. Urra H, Dufey E, Avril T, Chevet E, Hetz C (2016) Endoplasmic reticulum stress and the hallmarks of cancer. Trends in Cancer 2(5):252–262CrossRefGoogle Scholar
  181. Volkmann K, Lucas JL, Vuga D, Wang X, Brumm D, Stiles C, Kriebel D, Der-Sarkissian A, Krishnan K, Schweitzer C, Liu Z, Malyankar UM, Chiovitti D, Canny M, Durocher D, Sicheri F, Patterson JB (2011) Potent and selective inhibitors of the inositol-requiring enzyme 1 endoribonuclease. J Biol Chem 286(14):12743–12755. doi: 10.1074/jbc.M110.199737 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  182. Walter P, Ron D (2011) The unfolded protein response: from stress pathway to homeostatic regulation. Science 334(6059):1081–1086. doi: 10.1126/science.1209038 334/6059/1081 [pii]CrossRefGoogle Scholar
  183. Wang L, Perera BG, Hari SB, Bhhatarai B, Backes BJ, Seeliger MA, Schurer SC, Oakes SA, Papa FR, Maly DJ (2012a) Divergent allosteric control of the IRE1alpha endoribonuclease using kinase inhibitors. Nat Chem Biol 8(12):982–989. doi: 10.1038/nchembio.1094CrossRefPubMedPubMedCentralGoogle Scholar
  184. Wang Y, Alam GN, Ning Y, Visioli F, Dong Z, Nor JE, Polverini PJ (2012b) The unfolded protein response induces the angiogenic switch in human tumor cells through the PERK/ATF4 pathway. Cancer Res 72(20):5396–5406. doi: 10.1158/0008-5472.CAN-12-0474CrossRefPubMedPubMedCentralGoogle Scholar
  185. Wang ZV, Deng Y, Gao N, Pedrozo Z, Li DL, Morales CR, Criollo A, Luo X, Tan W, Jiang N, Lehrman MA, Rothermel BA, Lee AH, Lavandero S, Mammen PP, Ferdous A, Gillette TG, Scherer PE, Hill JA (2014) Spliced X-box binding protein 1 couples the unfolded protein response to hexosamine biosynthetic pathway. Cell 156(6):1179–1192. doi: 10.1016/j.cell.2014.01.014 S0092-8674(14)00025-7 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  186. Wheeler MC, Rizzi M, Sasik R, Almanza G, Hardiman G, Zanetti M (2008) KDEL-retained antigen in B lymphocytes induces a proinflammatory response: a possible role for endoplasmic reticulum stress in adaptive T cell immunity. J Immunol 181(1):256–264CrossRefGoogle Scholar
  187. Xue Z, He Y, Ye K, Gu Z, Mao Y, Qi L (2011) A conserved structural determinant located at the interdomain region of mammalian inositol-requiring enzyme 1{alpha}. J Biol Chem 286:30859–30866. doi: 10.1074/jbc.M111.273714CrossRefPubMedPubMedCentralGoogle Scholar
  188. Yacoub A, Hamed HA, Allegood J, Mitchell C, Spiegel S, Lesniak MS, Ogretmen B, Dash R, Sarkar D, Broaddus WC, Grant S, Curiel DT, Fisher PB, Dent P (2010) PERK-dependent regulation of ceramide synthase 6 and thioredoxin play a key role in mda-7/IL-24-induced killing of primary human glioblastoma multiforme cells. Cancer Res 70(3):1120–1129. doi: 10.1158/0008-5472.CAN-09-4043CrossRefPubMedPubMedCentralGoogle Scholar
  189. Yamamori T, Meike S, Nagane M, Yasui H, Inanami O (2013) ER stress suppresses DNA double-strand break repair and sensitizes tumor cells to ionizing radiation by stimulating proteasomal degradation of Rad51. FEBS Lett 587(20):3348–3353. doi: 10.1016/j.febslet.2013.08.030 S0014-5793(13)00659-5 [pii]CrossRefPubMedGoogle Scholar
  190. Yamamoto K, Sato T, Matsui T, Sato M, Okada T, Yoshida H, Harada A, Mori K (2007) Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1. Dev Cell 13(3):365–376CrossRefGoogle Scholar
  191. Yan D, Wang HW, Bowman RL, Joyce JA (2016) STAT3 and STAT6 signaling pathways synergize to promote cathepsin secretion from macrophages via IRE1alpha activation. Cell Rep 16(11):2914–2927. doi: 10.1016/j.celrep.2016.08.035CrossRefPubMedPubMedCentralGoogle Scholar
  192. Yang C, Huntoon K, Ksendzovsky A, Zhuang Z, Lonser RR (2013) Proteostasis modulators prolong missense VHL protein activity and halt tumor progression. Cell Rep 3(1):52–59. doi: 10.1016/j.celrep.2012.12.007CrossRefPubMedPubMedCentralGoogle Scholar
  193. Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, Brown MS, Goldstein JL (2000) ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell 6(6):1355–1364 S1097-2765(00)00133-7 [pii]CrossRefGoogle Scholar
  194. Yoshida H, Okada T, Haze K, Yanagi H, Yura T, Negishi M, Mori K (2000) ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Mol Cell Biol 20(18):6755–6767CrossRefGoogle Scholar
  195. Zeindl-Eberhart E, Brandl L, Liebmann S, Ormanns S, Scheel SK, Brabletz T, Kirchner T, Jung A (2014) Epithelial-mesenchymal transition induces endoplasmic-reticulum-stress response in human colorectal tumor cells. PLoS ONE 9(1):e87386. doi: 10.1371/journal.pone.0087386 PONE-D-13-31507 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  196. Zhang W, Hietakangas V, Wee S, Lim SC, Gunaratne J, Cohen SM (2013) ER stress potentiates insulin resistance through PERK-mediated FOXO phosphorylation. Genes Dev 27(4):441–449. doi: 10.1101/gad.201731.112 27/4/441 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  197. Zhou Y, Lee J, Reno CM, Sun C, Park SW, Chung J, Fisher SJ, White MF, Biddinger SB, Ozcan U (2011) Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction. Nat Med 17(3):356–365. doi: 10.1038/nm.2293 nm.2293 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  198. Zhu H, Chen X, Chen B, Song W, Sun D, Zhao Y (2014) Activating transcription factor 4 promotes esophageal squamous cell carcinoma invasion and metastasis in mice and is associated with poor prognosis in human patients. PLoS ONE 9(7):e103882. doi: 10.1371/journal.pone.0103882CrossRefPubMedPubMedCentralGoogle Scholar
  199. Zinszner H, Kuroda M, Wang X, Batchvarova N, Lightfoot RT, Remotti H, Stevens JL, Ron D (1998) CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev 12(7):982–995CrossRefGoogle Scholar
  200. Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G (2013) Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity 39(1):74–88. doi: 10.1016/j.immuni.2013.06.014 S1074-7613(13)00281-1 [pii]CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Inserm U1242 «Chemistry, Oncogenesis, Stress and Signaling»University of Rennes 1RennesFrance
  2. 2.Centre de Lutte contre le Cancer Eugène MarquisRennesFrance

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