Skip to main content

Advertisement

Log in

The STK38–XPO1 axis, a new actor in physiology and cancer

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

The Hippo signal transduction pathway is an essential regulator of organ size during developmental growth by controlling multiple cellular processes such as cell proliferation, cell death, differentiation, and stemness. Dysfunctional Hippo signaling pathway leads to dramatic tissue overgrowth. Here, we will briefly introduce the Hippo tumor suppressor pathway before focusing on one of its members and the unexpected twists that followed our quest of its functions in its multifarious actions beside the Hippo pathway: the STK38 kinase. In this review, we will precisely discuss the newly identified role of STK38 on regulating the nuclear export machinery by phosphorylating and activating, the major nuclear export receptor XPO1. Finally, we will phrase STK38′s role on regulating the subcellular distribution of crucial cellular regulators such as Beclin1 and YAP1 with its implication in cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Moon S, Yeon Park S, Woo Park H (2018) Regulation of the Hippo pathway in cancer biology. Cell Mol Life Sci 75:2303–2319

    Article  CAS  PubMed  Google Scholar 

  2. Yu FX, Guan KL (2013) The Hippo pathway: regulators and regulations. Genes Dev 27:355–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Pan D (2010) The hippo signaling pathway in development and cancer. Dev Cell 19:491–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ma S, Meng Z, Chen R, Guan K-L (2019) The hippo pathway: biology and pathophysiology. Annu Rev Biochem 88:577–604

    Article  CAS  PubMed  Google Scholar 

  5. Huang J, Wu S, Barrera J, Matthews K, Pan D (2005) The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila homolog of YAP. Cell 122:421–434

    Article  CAS  PubMed  Google Scholar 

  6. Hong W, Guan KL (2012) The YAP and TAZ transcription co-activators: Key downstream effectors of the mammalian Hippo pathway. Semin Cell Dev Biol 23:785–793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Moroishi T, Hansen CG, Guan KL (2015) The emerging roles of YAP and TAZ in cancer. Nat Rev Cancer 15:73–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Meng Z, Moroishi T, Guan KL (2016) Mechanisms of Hippo pathway regulation. Genes Dev 30:1–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Piccolo S, Dupont S, Cordenonsi M (2014) The biology of YAP/TAZ: Hippo signaling and beyond. Physiol Rev 94:1287–1312

    Article  CAS  PubMed  Google Scholar 

  10. Zanconato F, Cordenonsi M, Piccolo S (2016) YAP/TAZ at the Roots of Cancer. Cancer Cell 29:783–803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhao B, Li L, Lu Q, Wang LH, Liu CY, Lei Q, Guan KL (2011) Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev 25:51–63

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez JR, Zhou D, Kreger BT, Vasioukhin V, Avruch J, Brummelkamp TR et al (2011) Yap1 acts downstream of α-catenin to control epidermal proliferation. Cell 144:782–795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Dobrokhotov O, Samsonov M, Sokabe M, Hirata H (2018) Mechanoregulation and pathology of YAP/TAZ via Hippo and non-Hippo mechanisms. Clin Transl Med 7:23

    Article  PubMed  PubMed Central  Google Scholar 

  14. Dubois F, Keller M, Calvayrac O, Soncin F, Hoa L, Hergovich A, Parrini MC, Mazières J, Vaisse-Lesteven M, Camonis J et al (2016) RASSF1A suppresses the invasion and metastatic potential of human non-small cell lung cancer cells by inhibiting YAP activation through the GEF-H1/RhoB Pathway. Cancer Res 76:1627–1640

    Article  CAS  PubMed  Google Scholar 

  15. Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, Zhao J, Yuan H, Tumaneng K, Li H et al (2012) Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 150:780–791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kim MH, Kim J (2017) Role of YAP/TAZ transcriptional regulators in resistance to anti-cancer therapies. Cell Mol Life Sci 74:1457–1474

    Article  CAS  PubMed  Google Scholar 

  17. Wang W, Xiao ZD, Li X, Aziz KE, Gan B, Johnson RL, Chen J (2015) AMPK modulates Hippo pathway activity to regulate energy homeostasis. Nat Cell Biol 17:490–499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wang Z, Wu Y, Wang H, Zhang Y, Mei L, Fang X, Zhang X, Zhang F, Chen H, Liu Y et al (2014) Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility. Proc Natl Acad Sci USA 111:E89

    CAS  PubMed  Google Scholar 

  19. Liu B, Zheng Y, Yin F, Yu J, Silverman N, Pan D (2016) Toll receptor-mediated hippo signaling controls innate immunity in Drosophila. Cell 164:406–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Selimoglu R, Bettoun A, Joffre C, Meunier B, Parrini MC, Fesquet D, Formstecher E, Cascone I, Hergovich A, Camonis JH (2014) RalA GTPase and MAP4K4 function through NDR1 activation in stress response and apoptotic signaling. HSOA J Cell Biol Cell Metab 1:1–11

    Google Scholar 

  21. Meng Z, Moroishi T, Mottier-Pavie V, Plouffe SW, Hansen CG, Hong AW, Park HW, Mo JS, Lu W, Lu S et al (2015) MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway. Nat Commun 6:1

    Google Scholar 

  22. Zhang L, Tang F, Terracciano L, Hynx D, Kohler R, Bichet S, Hess D, Cron P, Hemmings BA, Hergovich A et al (2015) NDR functions as a physiological YAP1 kinase in the intestinal epithelium. Curr Biol 25:296–305

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science (80-) 298:1912–1934

    Article  CAS  Google Scholar 

  24. Hergovich A, Stegert MR, Schmitz D, Hemmings BA (2006) NDR kinases regulate essential cell processes from yeast to humans. Nat Rev Mol Cell Biol 7:253–264

    Article  CAS  PubMed  Google Scholar 

  25. Bichsel SJ, Tamaskovic R, Stegert MR, Hemmings BA (2004) Mechanism of activation of NDR (nuclear Dbf2-related) protein kinase by the hMOB1 protein. J Biol Chem 279:35228–35235

    Article  CAS  PubMed  Google Scholar 

  26. Tamaskovic R, Bichsel SJ, Rogniaux H, Stegert MR, Hemmings BA (2003) Mechanism of Ca2+-mediated regulation of NDR protein kinase through autophosphorylation and phosphorylation by an upstream kinase. J Biol Chem 278:6710–6718

    Article  CAS  PubMed  Google Scholar 

  27. Stegert MR, Tamaskovic R, Bichsel SJ, Hergovich A, Hemmings BA (2004) Regulation of NDR2 protein kinase by multi-site phosphorylation and the S100B calcium-binding protein. J Biol Chem 279:23806–23812

    Article  CAS  PubMed  Google Scholar 

  28. Millward TA, Hess D, Hemmings BA (1999) Ndr protein kinase is regulated by phosphorylation on two conserved sequence motifs. J Biol Chem 274:33847–33850

    Article  CAS  PubMed  Google Scholar 

  29. Stegert MR, Hergovich A, Tamaskovic R, Bichsel SJ, Hemmings BA (2005) Regulation of NDR protein kinase by hydrophobic motif phosphorylation mediated by the mammalian Ste20-like kinase MST3. Mol Cell Biol 25:11019–11029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Xiong S, Lorenzen K, Couzens AL, Templeton CM, Rajendran D, Mao DYL, Juang YC, Chiovitti D, Kurinov I, Guettler S et al (2018) Structural basis for auto-inhibition of the NDR1 kinase domain by an atypically long activation segment. Structure 26:1101-1115.e6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hergovich A (2016) The Roles of NDR protein kinases in hippo signalling. Genes (Basel) 7:21

    Article  CAS  Google Scholar 

  32. Hergovich A (2013) Regulation and functions of mammalian LATS/NDR kinases: Looking beyond canonical Hippo signalling. Cell Biosci 3:32

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Hergovich A, Kohler RS, Schmitz D, Vichalkovski A, Cornils H, Hemmings BA (2009) The MST1 and hMOB1 tumor suppressors control human centrosome duplication by regulating NDR kinase phosphorylation. Curr Biol 19:1692–1702

    Article  CAS  PubMed  Google Scholar 

  34. Vichalkovski A, Gresko E, Cornils H, Hergovich A, Schmitz D, Hemmings BA (2008) NDR kinase is activated by RASSF1A/MST1 in response to fas receptor stimulation and promotes apoptosis. Curr Biol 18:1889–1895

    Article  CAS  PubMed  Google Scholar 

  35. Cornils H, Kohler RS, Hergovich A, Hemmings BA (2011a) Human NDR kinases control G1/S cell cycle transition by directly regulating p21 stability. Mol Cell Biol 31:1382–1395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wu B, Guo W (2015) The exocyst at a glance. J Cell Sci 128:2957–2964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Martin-Urdiroz M, Deeks MJ, Horton CG, Dawe HR, Jourdain I (2016) The exocyst complex in health and disease. Front Cell Dev Biol 4:1–22

    Article  Google Scholar 

  38. Hoa L, Kulaberoglu Y, Gundogdu R, Cook D, Mavis M, Gomez M, Gomez V, Hergovich A (2016) The characterisation of LATS2 kinase regulation in Hippo-YAP signalling. Cell Signal 28:488–497

    Article  CAS  PubMed  Google Scholar 

  39. Mah AS, Jang J, Deshaies RJ (2001) Protein kinase Cdc15 activates the Dbf2-Mob1 kinase complex. Proc Natl Acad Sci USA 98:7325–7330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Emoto K, He Y, Ye B, Grueber WB, Adler PN, Jan LY, Jan YN (2004) Control of dendritic branching and tiling by the tricornered-kinase/furry signaling pathway in Drosophila sensory neurons. Cell 119:245–256

    Article  CAS  PubMed  Google Scholar 

  41. He Y, Fang X, Emoto K, Jan YN, Adler PN (2005) The tricornered Ser/Thr protein kinase is regulated by phosphorylation and interacts with furry during Drosophila wing hair development. Mol Biol Cell 16:689–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chan EHY, Nousiainen M, Chalamalasetty RB, Schäfer A, Nigg EA, Sillje HHW (2005) The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene 24:2076–2086

    Article  CAS  PubMed  Google Scholar 

  43. Martin AP, Jacquemyn M, Lipecka J, Chhuon C, Aushev VN, Meunier B, Singh MK, Carpi N, Piel M, Codogno P et al (2019) STK38 kinase acts as XPO1 gatekeeper regulating the nuclear export of autophagy proteins and other cargoes. EMBO Rep 20:e48150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cook D, Hoa LY, Gomez V, Gomez M, Hergovich A (2014) Constitutively active NDR1-PIF kinase functions independent of MST1 and hMOB1 signalling. Cell Signal 26:1657–1667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hergovich A, Bichsel SJ, Hemmings BA (2005) Human NDR kinases are rapidly activated by mob proteins through recruitment to the plasma membrane and phosphorylation. Mol Cell Biol 25:8259–8272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hergovich A (2011) MOB control: reviewing a conserved family of kinase regulators. Cell Signal 23:1433–1440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Bothos J, Tuttle RL, Ottey M, Luca FC, Halazonetis TD (2005) Human LATS1 is a mitotic exit network kinase. Cancer Res 65:6568–6575

    Article  CAS  PubMed  Google Scholar 

  48. Hou M-C, Guertin DA, McCollum D (2004) Initiation of cytokinesis is controlled through multiple modes of regulation of the Sid2p-Mob1p kinase complex. Mol Cell Biol 24:3262–3276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kohler RS, Schmitz D, Cornils H, Hemmings BA, Hergovich A (2010) Differential NDR/LATS interactions with the human MOB family reveal a negative role for human MOB2 in the regulation of human NDR kinases. Mol Cell Biol 30:4507–4520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Parker B, Gogl G, Bálint M, Hetenyi C, Remenyi A, Weiss EL (2020) Ndr/Lats kinases bind specific Mob-family coactivators through a conserved and modular interface. Biochemistry 59:1688

    Article  CAS  PubMed  Google Scholar 

  51. Gallegos ME, Bargmann CI (2004) Mechanosensory neurite termination and tiling depend on SAX-2 and the SAX-1 kinase. Neuron 44:239–249

    Article  CAS  PubMed  Google Scholar 

  52. Chiba S, Ikeda M, Katsunuma K, Ohashi K, Mizuno K (2009) MST2- and furry-mediated activation of NDR1 kinase is critical for precise alignment of mitotic chromosomes. Curr Biol 19:675–681

    Article  CAS  PubMed  Google Scholar 

  53. Hergovich A, Cornils H, Hemmings BA (2008) Mammalian NDR protein kinases: From regulation to a role in centrosome duplication. Biochim Biophys Acta Proteins Proteomics 1784:3–15

    Article  CAS  Google Scholar 

  54. Schmitz-Rohmer D, Probst S, Yang ZZ, Laurent F, Stadler MB, Zuniga A, Zeller R, Hynx D, Hemmings BA, Hergovich A (2015) NDR kinases are essential for somitogenesis and cardiac looping during mouse embryonic development. PLoS ONE 10:e0136566

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Cornils H, Stegert MR, Hergovich A, Hynx D, Schmitz D, Dirnhofer S, Hemmings BA (2010) Ablation of the kinase NDR1 predisposes mice to the development of T cell lymphoma. Sci Signal 3:ra47

    Article  PubMed  CAS  Google Scholar 

  56. Johnson LN, Noble MEM, Owen DJ (1996) Active and inactive protein kinases: structural basis for regulation. Cell 85:149–158

    Article  CAS  PubMed  Google Scholar 

  57. Hergovich A, Lamla S, Nigg EA, Hemmings BA (2007) Centrosome-associated NDR kinase regulates centrosome duplication. Mol Cell 25:625–634

    Article  CAS  PubMed  Google Scholar 

  58. Cornils H, Kohler RS, Hergovich A, Hemmings BA (2011b) Downstream of human NDR kinases: impacting on c-myc and p21 protein stability to control cell cycle progression. Cell Cycle 10:1897–1904

    Article  CAS  PubMed  Google Scholar 

  59. Du Z, Tong X, Ye X (2013) Cyclin D1 promotes cell cycle progression through enhancing NDR1/2 kinase activity independent of cyclin-dependent kinase. J Biol Chem 288:26678–26687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Adhikary S, Eilers M (2005) Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 6:635–645

    Article  CAS  PubMed  Google Scholar 

  61. Bisikirska BC, Adam SJ, Alvarez MJ, Rajbhandari P, Cox R, Lefebvre C, Wang K, Rieckhof GE, Felsher DW, Califano A (2013) STK38 is a critical upstream regulator of MYC’s oncogenic activity in human B-cell lymphoma. Oncogene 32:5283–5291

    Article  CAS  PubMed  Google Scholar 

  62. Keller M, Dubois F, Teulier S, Martin APJ, Levallet J, Maille E, Brosseau S, Elie N, Hergovich A, Bergot E et al (2019) NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells. J Exp Clin Cancer Res 38:1

    Article  Google Scholar 

  63. Gomez V, Gundogdu R, Gomez M, Hoa L, Panchal N, O’Driscoll M, Hergovich A (2015) Regulation of DNA damage responses and cell cycle progression by hMOB2. Cell Signal 27:326–339

    Article  CAS  PubMed  Google Scholar 

  64. Park JM, Choi JY, Yi JM, Chung JW, Leem SH, Koh SS, Kang TH (2015) NDR1 modulates the UV-induced DNA-damage checkpoint and nucleotide excision repair. Biochem Biophys Res Commun 461:543–548

    Article  CAS  PubMed  Google Scholar 

  65. Enomoto A, Fukasawa T, Takamatsu N, Ito M, Morita A, Hosoi Y, Miyagawa K (2013) The HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin modulates radiosensitivity by downregulating serine/threonine kinase 38 via Sp1 inhibition. Eur J Cancer 49:3547–3558

    Article  CAS  PubMed  Google Scholar 

  66. Fukasawa T, Enomoto A, Miyagawa K (2015) Serine-Threonine Kinase 38 regulates CDC25A stability and the DNA damage-induced G2/M checkpoint. Cell Signal 27:1569–1575

    Article  CAS  PubMed  Google Scholar 

  67. Sharif AAD, Hergovich A (2018) The NDR/LATS protein kinases in immunology and cancer biology. Semin Cancer Biol 48:104–114

    Article  CAS  PubMed  Google Scholar 

  68. Tang F, Gill J, Ficht X, Barthlott T, Cornils H, Schmitz-Rohmer D, Hynx D, Zhou D, Zhang L, Xue G et al (2015) The kinases NDR1/2 act downstream of the Hippo homolog MST1 to mediate both egress of thymocytes from the thymus and lymphocyte motility. Sci Signal 8:ra100

    PubMed  Google Scholar 

  69. Devroe E, Silver PA, Engelman A (2005) HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases. Virology 331:181–189

    Article  CAS  PubMed  Google Scholar 

  70. Atkins C, Evans CW, Nordin B, Patricelli MP, Reynolds R, Wennerberg K, Noah JW (2014) Global human-kinase screening identifies therapeutic host targets against influenza. J Biomol Screen 19:936–946

    Article  PubMed  CAS  Google Scholar 

  71. Liu Z, Qin Q, Wu C, Li H, Shou J, Yang Y, Gu M, Ma C, Lin W, Zou Y et al (2018) Downregulated NDR1 protein kinase inhibits innate immune response by initiating an miR146a-STAT1 feedback loop. Nat Commun 9:1

    Article  CAS  Google Scholar 

  72. Messina M, Chiaretti S, Tavolaro S, Peragine N, Vitale A, Elia L, Sica S, Levis A, Guarini A, Foà R (2010) Protein kinase gene expression profiling and in vitro functional experiments identify novel potential therapeutic targets in adult acute lymphoblastic leukemia. Cancer 116:3426–3437

    Article  CAS  PubMed  Google Scholar 

  73. Joffre C, Dupont N, Hoa L, Gomez V, Pardo R, Gonçalves-Pimentel C, Achard P, Bettoun A, Meunier B, Bauvy C et al (2015) The pro-apoptotic STK38 kinase is a new Beclin1 partner positively regulating autophagy. Curr Biol 25:2479–2492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Joffre C, Codogno P, Fanto M, Hergovich A, Camonis J (2016) STK38 at the crossroad between autophagy and apoptosis. Autophagy 12:594–595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wu Z, Sawada T, Shiba K, Liu S, Kanao T, Takahashi R, Hattori N, Imai Y, Lu B (2013) Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance. Genes Dev 27:157–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Bettoun A, Joffre C, Zago G, Surdez D, Vallerand D, Gundogdu R, Sharif AAD, Gomez M, Cascone I, Meunier B et al (2016) Mitochondrial clearance by the STK38 kinase supports oncogenic Ras-induced cell transformation. Oncotarget 7:44142–44160

    Article  PubMed  PubMed Central  Google Scholar 

  77. Lam SS, Martell JD, Kamer KJ, Deerinck TJ, Ellisman MH, Mootha VK, Ting AY (2014) Directed evolution of APEX2 for electron microscopy and proximity labeling. Nat Methods 12:51–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Hao Y, Chun A, Cheung K, Rashidi B, Yang X (2008) Tumor suppressor LATS1 is a negative regulator of oncogene YAP. J Biol Chem 283:5496–5509

    Article  CAS  PubMed  Google Scholar 

  79. Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, Xie J, Ikenoue T, Yu J, Li L et al (2007) Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev 21:2747–2761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shi DD, Shi H, Lu D, Li R, Zhang Y, Zhang J (2012) NDR1/STK38 potentiates NF-κB activation by its kinase activity. Cell Biochem Funct 30:664–670

    Article  CAS  PubMed  Google Scholar 

  81. Paul I, Batth TS, Iglesias-Gato D, Al-Araimi A, Al-Haddabi I, Alkharusi A, Norstedt G, Olsen JV, Zadjali F, Flores-Morales A (2017) The ubiquitin ligase Cullin5 SOCS2 regulates NDR1/STK38 stability and NF-κB transactivation. Sci Rep 7:42800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Pot I, Patel S, Deng L, Chandhoke AS, Zhang C, Bonni A, Bonni S (2013) Identification of a novel link between the protein kinase NDR1 and TGFβ signaling in epithelial cells. PLoS ONE 8:e67178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Rashidian J, Le Scolan E, Ji X, Zhu Q, Mulvihill MM, Nomura D, Luo K (2015) Ski regulates hippo and TAZ signaling to suppress breast cancer progression. Sci Signal 8:ra14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Koike-Kumagai M, Yasunaga KI, Morikawa R, Kanamori T, Emoto K (2009) The target of rapamycin complex 2 controls dendritic tiling of drosophila sensory neurons through the tricornered kinase signalling pathway. EMBO J28:3879–3892

    Article  CAS  Google Scholar 

  85. Adeyinka A, Emberley E, Niu Y, Snell L, Murphy LC, Sowter H, Wykoff CC, Harris AL, Watson PH (2002) Analysis of gene expression in ductal carcinoma in situ of the breast. Clin Cancer Res 8:3788–3795

    CAS  PubMed  Google Scholar 

  86. Welsh JB, Zarrinkar PP, Sapinoso LM, Kern SG, Behling CA, Monk BJ, Lockhart DJ, Burger RA, Hampton GM (2001) Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer. Proc Natl Acad Sci USA 98:1176–1181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Lu KH, Patterson AP, Wang L, Marquez RT, Atkinson EN, Baggerly KA, Ramoth LR, Rosen DG, Liu J, Hellstrom I et al (2004) Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis. Clin Cancer Res 10:3291–3300

    Article  CAS  PubMed  Google Scholar 

  88. Garber ME, Troyanskaya OG, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M, Van De Rijn M, Rosen GD, Perou CM, Whyte RI et al (2001) Diversity of gene expression in adenocarcinoma of the lung. Proc Natl Acad Sci USA 98:13784–13789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Bhattacharjee A, Richards WG, Staunton J, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M et al (2001) Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA 98:13790–13795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Mor A, White MA, Fontoura BMA (2014) Nuclear trafficking in health and disease. Curr Opin Cell Biol 28:28–35

    Article  CAS  PubMed  Google Scholar 

  91. Hung MC, Link W (2011) Protein localization in disease and therapy. J Cell Sci 124:3381–3392

    Article  CAS  PubMed  Google Scholar 

  92. Hill R, Cautain B, De Pedro N, Link W (2014) Targeting nucleocytoplasmic transport in cancer therapy. Oncotarget 5:11–28

    Article  PubMed  Google Scholar 

  93. Yu YP, Landsittel D, Jing L, Nelson J, Ren B, Liu L, McDonald C, Thomas R, Dhir R, Finkelstein S et al (2004) Gene expression alterations in prostate cancer predicting tumor aggression and preceding development of malignancy. J Clin Oncol 22:2790–2799

    Article  CAS  PubMed  Google Scholar 

  94. Eder IE, Bektic J, Haag P, Bartsch G, Klocker H (2004) Genes differentially expressed in prostate cancer. BJU Int 93:1151–1155

    Article  CAS  PubMed  Google Scholar 

  95. Lapointe J, Li C, Higgins JP, Van De Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U et al (2004) Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci USA 101:811–816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Hummerich L, Müller R, Hess J, Kokocinski F, Hahn M, Fürstenberger G, Mauch C, Lichter P, Angel P (2006) Identification of novel tumour-associated genes differentially expressed in the process of squamous cell cancer development. Oncogene 25:111–121

    Article  CAS  PubMed  Google Scholar 

  97. Cui DX, Zhang L, Yan XJ, Zhang LX, Xu JR, Guo YH, Jin GQ, Gomez G, Li D, Zhao JR et al (2005) A microarray-based gastric carcinoma prewarning system. World J Gastroenterol 11:1273–1282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Liang XH, Yu J, Brown K, Levine B (2001) Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function beclin 1 contains a leucine-rich nuclear export signal that is required for its. Cancer Res 61:3443–3449

    CAS  PubMed  Google Scholar 

  99. Kim J, Mcmillan E, Kim HS, Venkateswaran N, Makkar G, Rodriguez-canales J, Villalobos P, Neggers JE, Mendiratta S, Wei S et al (2016) XPO1-dependent nuclear export is a druggable vulnerability in KRAS-mutant lung cancer. Nature 538:114–117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Subhash VV, Yeo MS, Wang L, Tan SH, Wong FY, Thuya WL, Tan WL, Peethala PC, Soe MY, Tan DSP et al (2018) Anti-tumor efficacy of Selinexor (KPT-330) in gastric cancer is dependent on nuclear accumulation of p53 tumor suppressor. Sci Rep 8:1–10

    Article  CAS  Google Scholar 

  101. Kirli K, Karaca S, Dehne HJ, Samwer M, Pan KT, Lenz C, Urlaub H, Gorlich D (2015) A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. Elife 4:1–28

    Article  Google Scholar 

  102. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z (2017) GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res 45:W98–W102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank our collaborators who participated in this work with inventive ideas, in particular: A. Hergovitch from UC; MK Singh from Paris; MC. Parrini, and B. Meunier from Institut Curie Paris; V. Aushev from Mount Sinai New-York; P. Codogno and C. Guerera and her collaborators from the mass spectrometry platform of INEM Paris; N. Carpi and M. Piel from IPGG Paris; and D. Daelemans and M. Jacquemyn from KU Leuven. We also apologize to colleagues whose work was not cited because of the space limitations of this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alexandre PJ. Martin.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Martin, A.P., Aushev, V.N., Zalcman, G. et al. The STK38–XPO1 axis, a new actor in physiology and cancer. Cell. Mol. Life Sci. 78, 1943–1955 (2021). https://doi.org/10.1007/s00018-020-03690-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-020-03690-w

Keywords

Navigation