IP3 Receptor Biology and Endoplasmic Reticulum Calcium Dynamics in Cancer

Parys, Jan B.; Bultynck, Geert; Vervliet, Tim

doi:10.1007/978-3-030-67696-4_11

Jan B. Parys⁶,
Geert Bultynck⁶ &
Tim Vervliet⁶

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 59))

2477 Accesses
10 Citations

Abstract

Intracellular Ca²⁺ signaling regulates a plethora of cellular functions. A central role in these processes is reserved for the inositol 1,4,5-trisphosphate receptor (IP₃R), a ubiquitously expressed Ca²⁺-release channel, mainly located in the endoplasmic reticulum (ER). Three IP₃R isoforms (IP₃R1, IP₃R2 and IP₃R3) exist, encoded respectively by ITPR1, ITPR2 and ITPR3. The proteins encoded by these genes are each about 2700 amino acids long and assemble into large tetrameric channels, which form the target of many regulatory proteins, including several tumor suppressors and oncogenes. Due to the important role of the IP₃Rs in cell function, their dysregulation is linked to multiple pathologies. In this review, we highlight the complex role of the IP₃R in cancer, as it participates in most of the so-called “hallmarks of cancer”. In particular, the IP₃R directly controls cell death and cell survival decisions via regulation of autophagy and apoptosis. Moreover, the IP₃R impacts cellular proliferation, migration and invasion. Typical examples of the role of the IP₃Rs in these various processes are discussed. The relative levels of the IP₃R isoforms expressed and their subcellular localization, e.g. at the ER-mitochondrial interface, is hereby important. Finally, evidence is provided about how the knowledge of the regulation of the IP₃R by tumor suppressors and oncogenes can be exploited to develop novel therapeutic approaches to fight cancer.

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Abbreviations

AMPK:: Adenosine monophosphate-activated protein kinase
APAF1:: Apoptotic protease-activating factor 1
ARM:: Armadillo solenoid fold
ATG:: Autophagy-related
BK_Ca Channel:: large conductance Ca²⁺-activated K⁺ channel
ER:: Endoplasmic reticulum
IICR:: IP₃-induced Ca²⁺ release
IP₃:: Inositol 1,4,5-trisphosphate
IP₃R:: Inositol 1,4,5-trisphosphate receptor
ITPR:: Inositol 1,4,5-trisphosphate receptor gene
MOMP:: Mitochondrial outer membrane permeabilization
mPTP:: Mitochondrial permeability transition pore
mTORC1:: Mechanistic target of rapamycin complex 1
ROS:: Reactive oxygen species
SMAC:: Second mitochondria-derived activator of caspases
SOCE:: Store-operated Ca²⁺ entry
XIAP:: X-linked inhibitor of apoptosis protein

References

Akl H, Monaco G, La Rovere R, Welkenhuyzen K, Kiviluoto S et al (2013) IP₃R2 levels dictate the apoptotic sensitivity of diffuse large B-cell lymphoma cells to an IP₃R-derived peptide targeting the BH4 domain of Bcl-2. Cell Death Dis 4:e632. https://doi.org/10.1038/cddis.2013.140
Article CAS PubMed PubMed Central Google Scholar
Akl H, La Rovere RM, Janssens A, Vandenberghe P, Parys JB et al (2015) HA14-1 potentiates apoptosis in B-cell cancer cells sensitive to a peptide disrupting IP₃ receptor/Bcl-2 complexes. Int J Dev Biol 59(7–9):391–398. https://doi.org/10.1387/ijdb.150213gb
Article CAS PubMed Google Scholar
Alonso MT, Garcia-Sancho J (2011) Nuclear Ca²⁺ signalling. Cell Calcium 49(5):280–289. https://doi.org/10.1016/j.ceca.2010.11.004
Article CAS PubMed Google Scholar
Alzayady KJ, Wang L, Chandrasekhar R, Wagner LE II, Van Petegem F et al (2016) Defining the stoichiometry of inositol 1,4,5-trisphosphate binding required to initiate Ca²⁺ release. Sci Signal 9(422):ra35. https://doi.org/10.1126/scisignal.aad6281
Article CAS PubMed PubMed Central Google Scholar
Arrington AK, Heinrich EL, Lee W, Duldulao M, Patel S et al (2012) Prognostic and predictive roles of KRAS mutation in colorectal cancer. Int J Mol Sci 13(10):12153–12168. https://doi.org/10.3390/ijms131012153
Article CAS PubMed PubMed Central Google Scholar
Atakpa P, Thillaiappan NB, Mataragka S, Prole DL, Taylor CW (2018) IP₃ receptors preferentially associate with ER-lysosome contact sites and selectively deliver Ca²⁺ to lysosomes. Cell Rep 25(11):3180–3193 e7. https://doi.org/10.1016/j.celrep.2018.11.064
Article CAS PubMed PubMed Central Google Scholar
Azumaya CM, Linton EA, Risener CJ, Nakagawa T, Karakas E (2020) Cryo-EM structure of human type-3 inositol triphosphate receptor reveals the presence of a self-binding peptide that acts as an antagonist. J Biol Chem 295(6):1743–1753. https://doi.org/10.1074/jbc.RA119.011570
Article CAS PubMed PubMed Central Google Scholar
Barnhart BC, Alappat EC, Peter ME (2003) The CD95 type I/type II model. Semin Immunol 15(3):185–193. https://doi.org/10.1016/s1044-5323(03)00031-9
Article CAS PubMed Google Scholar
Bartok A, Weaver D, Golenar T, Nichtova Z, Katona M et al (2019) IP₃ receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer. Nat Commun 10(1):3726. https://doi.org/10.1038/s41467-019-11646-3
Article CAS PubMed PubMed Central Google Scholar
Berridge MJ (2016) The inositol trisphosphate/calcium signaling pathway in health and disease. Physiol Rev 96(4):1261–1296. https://doi.org/10.1152/physrev.00006.2016
Article CAS PubMed Google Scholar
Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1(1):11–21. https://doi.org/10.1038/35036035
Article CAS PubMed Google Scholar
Bittremieux M, Parys JB, Pinton P, Bultynck G (2016) ER functions of oncogenes and tumor suppressors: Modulators of intracellular Ca²⁺ signaling. Biochim Biophys Acta 1863(6 Pt B):1364–1378. https://doi.org/10.1016/j.bbamcr.2016.01.002
Article CAS PubMed Google Scholar
Bittremieux M, La Rovere RM, Akl H, Martines C, Welkenhuyzen K et al (2019) Constitutive IP₃ signaling underlies the sensitivity of B-cell cancers to the Bcl-2/IP₃ receptor disruptor BIRD-2. Cell Death Differ 26(3):531–547. https://doi.org/10.1038/s41418-018-0142-3
Article CAS PubMed Google Scholar
Blackshaw S, Sawa A, Sharp AH, Ross CA, Snyder SH et al (2000) Type 3 inositol 1,4,5-trisphosphate receptor modulates cell death. FASEB J 14(10):1375–1379. https://doi.org/10.1096/fj.14.10.1375
Article CAS PubMed Google Scholar
Boehning D, Patterson RL, Sedaghat L, Glebova NO, Kurosaki T et al (2003) Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. Nat Cell Biol 5(12):1051–1061. https://doi.org/10.1038/ncb1063
Article PubMed Google Scholar
Bong AHL, Monteith GR (2018) Calcium signaling and the therapeutic targeting of cancer cells. Biochim Biophys Acta Mol Cell Res 1865(11 Pt B):1786–1794. https://doi.org/10.1016/j.bbamcr.2018.05.015
Article CAS PubMed Google Scholar
Bootman MD, Bultynck G (2020) Fundamentals of cellular calcium signaling: a primer. Cold Spring Harb Perspect Biol 12(1):a038802. https://doi.org/10.1101/cshperspect.a038802
Article CAS PubMed PubMed Central Google Scholar
Bootman MD, Chehab T, Bultynck G, Parys JB, Rietdorf K (2018) The regulation of autophagy by calcium signals: Do we have a consensus? Cell Calcium 70:32–46. https://doi.org/10.1016/j.ceca.2017.08.005
Article CAS PubMed Google Scholar
Bosanac I, Alattia JR, Mal TK, Chan J, Talarico S et al (2002) Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand. Nature 420(6916):696–700. https://doi.org/10.1038/nature01268
Article CAS PubMed Google Scholar
Bosanac I, Yamazaki H, Matsu-Ura T, Michikawa T, Mikoshiba K et al (2005) Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor. Mol Cell 17(2):193–203. https://doi.org/10.1016/j.molcel.2004.11.047
Article CAS PubMed Google Scholar
Cardenas C, Miller RA, Smith I, Bui T, Molgó J et al (2010) Essential regulation of cell bioenergetics by constitutive InsP₃ receptor Ca²⁺ transfer to mitochondria. Cell 142(2):270–283. https://doi.org/10.1016/j.cell.2010.06.007
Cardenas C, Muller M, McNeal A, Lovy A, Jana F et al (2016) Selective vulnerability of cancer cells by inhibition of Ca²⁺ transfer from endoplasmic reticulum to mitochondria. Cell Rep 14(10):2313–2324. https://doi.org/10.1016/j.celrep.2016.02.030
Article CAS PubMed PubMed Central Google Scholar
Carroll J, He J, Ding S, Fearnley IM, Walker JE (2019) Persistence of the permeability transition pore in human mitochondria devoid of an assembled ATP synthase. Proc Natl Acad Sci U S A 116(26):12816–12821. https://doi.org/10.1073/pnas.1904005116
Article CAS PubMed PubMed Central Google Scholar
Chen JJ, Boehning D (2017) Protein lipidation as a regulator of apoptotic calcium release: relevance to cancer. Front Oncol 7:138. https://doi.org/10.3389/fonc.2017.00138
Article PubMed PubMed Central Google Scholar
Csordas G, Thomas AP, Hajnoczky G (1999) Quasi-synaptic calcium signal transmission between endoplasmic reticulum and mitochondria. EMBO J 18(1):96–108. https://doi.org/10.1093/emboj/18.1.96
Article CAS PubMed PubMed Central Google Scholar
Cui C, Merritt R, Fu L, Pan Z (2017) Targeting calcium signaling in cancer therapy. Acta Pharm Sin B 7(1):3–17. https://doi.org/10.1016/j.apsb.2016.11.001
Article PubMed Google Scholar
Decuypere JP, Bultynck G, Parys JB (2011a) A dual role for Ca²⁺ in autophagy regulation. Cell Calcium 50(3):242–250. https://doi.org/10.1016/j.ceca.2011.04.001
Article CAS PubMed Google Scholar
Decuypere JP, Welkenhuyzen K, Luyten T, Ponsaerts R, Dewaele M et al (2011b) Ins(1,4,5)P3 receptor-mediated Ca²⁺ signaling and autophagy induction are interrelated. Autophagy 7(12):1472–1489. https://doi.org/10.4161/auto.7.12.17909
Article CAS PubMed PubMed Central Google Scholar
Dubois C, Prevarskaya N, Vanden Abeele F (2016) The calcium-signaling toolkit: updates needed. Biochim Biophys Acta 1863(6 Pt B):1337–1343. https://doi.org/10.1016/j.bbamcr.2015.11.033
Article CAS PubMed Google Scholar
Eskelinen EL (2011) The dual role of autophagy in cancer. Curr Opin Pharmacol 11(4):294–300. https://doi.org/10.1016/j.coph.2011.03.009
Article CAS PubMed Google Scholar
Feriod CN, Oliveira AG, Guerra MT, Nguyen L, Richards KM et al (2017) Hepatic inositol 1,4,5 trisphosphate receptor type 1 mediates fatty liver. Hepatol Commun 1(1):23–35. https://doi.org/10.1002/hep4.1012
Article CAS PubMed Google Scholar
Foskett JK, White C, Cheung KH, Mak DO (2007) Inositol trisphosphate receptor Ca²⁺ release channels. Physiol Rev 87(2):593–658. https://doi.org/10.1152/physrev.00035.2006
Article CAS PubMed Google Scholar
Fredericks GJ, Hoffmann FW, Rose AH, Osterheld HJ, Hess FM et al (2014) Stable expression and function of the inositol 1,4,5-triphosphate receptor requires palmitoylation by a DHHC6/selenoprotein K complex. Proc Natl Acad Sci U S A 111(46):16478–16483. https://doi.org/10.1073/pnas.1417176111
Article CAS PubMed PubMed Central Google Scholar
Galluzzi L, Vanpouille-Box C (2018) BAX and BAK at the gates of innate immunity. Trends Cell Biol 28(5):343–345. https://doi.org/10.1016/j.tcb.2018.02.010
Article CAS PubMed Google Scholar
Gambardella J, Lombardi A, Morelli MB, Ferrara J, Santulli G (2020) Inositol 1,4,5-trisphosphate receptors in human disease: a comprehensive update. J Clin Med 9(4):1096. https://doi.org/10.3390/jcm9041096
Article CAS PubMed Central Google Scholar
Giacomello M, Drago I, Bortolozzi M, Scorzeto M, Gianelle A et al (2010) Ca²⁺ hot spots on the mitochondrial surface are generated by Ca²⁺ mobilization from stores, but not by activation of store-operated Ca²⁺ channels. Mol Cell 38(2):280–290. https://doi.org/10.1016/j.molcel.2010.04.003
Article CAS PubMed Google Scholar
Giorgio V, Burchell V, Schiavone M, Bassot C, Minervini G et al (2017) Ca²⁺ binding to F-ATP synthase β subunit triggers the mitochondrial permeability transition. EMBO Rep 18(7):1065–1076. https://doi.org/10.15252/embr.201643354
Gordon PB, Holen I, Fosse M, Rotnes JS, Seglen PO (1993) Dependence of hepatocytic autophagy on intracellularly sequestered calcium. J Biol Chem 268(35):26107–26112
Article CAS PubMed Google Scholar
Greenberg EF, McColl KS, Zhong F, Wildey G, Dowlati A et al (2015) Synergistic killing of human small cell lung cancer cells by the Bcl-2-inositol 1,4,5-trisphosphate receptor disruptor BIRD-2 and the BH3-mimetic ABT-263. Cell Death Dis 6:e2034. https://doi.org/10.1038/cddis.2015.355
Article CAS PubMed PubMed Central Google Scholar
Guerra MT, Florentino RM, Franca A, Lima Filho AC, Dos Santos ML et al (2019) Expression of the type 3 InsP₃ receptor is a final common event in the development of hepatocellular carcinoma. Gut 68(9):1676–1687. https://doi.org/10.1136/gutjnl-2018-317811
Hamada K, Miyatake H, Terauchi A, Mikoshiba K (2017) IP₃-mediated gating mechanism of the IP₃ receptor revealed by mutagenesis and X-ray crystallography. Proc Natl Acad Sci U S A 114(18):4661–4666. https://doi.org/10.1073/pnas.1701420114
Article CAS PubMed PubMed Central Google Scholar
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013
Article CAS PubMed Google Scholar
Higo T, Hattori M, Nakamura T, Natsume T, Michikawa T et al (2005) Subtype-specific and ER lumenal environment-dependent regulation of inositol 1,4,5-trisphosphate receptor type 1 by ERp44. Cell 120(1):85–98. https://doi.org/10.1016/j.cell.2004.11.048
Article CAS PubMed Google Scholar
Hisatsune C, Mikoshiba K (2017) IP₃ receptor mutations and brain diseases in human and rodents. J Neurochem 141(6):790–807. https://doi.org/10.1111/jnc.13991
Article CAS PubMed Google Scholar
Hohendanner F, McCulloch AD, Blatter LA, Michailova AP (2014) Calcium and IP₃ dynamics in cardiac myocytes: experimental and computational perspectives and approaches. Front Pharmacol 5:35. https://doi.org/10.3389/fphar.2014.00035
Article CAS PubMed PubMed Central Google Scholar
Høyer-Hansen M, Bastholm L, Szyniarowski P, Campanella M, Szabadkai G et al (2007) Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-β, and Bcl-2. Mol Cell 25(2):193–205. https://doi.org/10.1016/j.molcel.2006.12.009
Hu YX, Han XS, Jing Q (2019) Ca²⁺ ion and autophagy. Adv Exp Med Biol 1206:151–166. https://doi.org/10.1007/978-981-15-0602-4_7
Article CAS PubMed Google Scholar
Huang X, Jin M, Chen YX, Wang J, Zhai K et al (2016) ERP44 inhibits human lung cancer cell migration mainly via IP₃R2. Aging (Albany NY) 8(6):1276–1286. https://doi.org/10.18632/aging.100984
Article CAS Google Scholar
Humeau J, Bravo-San Pedro JM, Vitale I, Nunez L, Villalobos C et al (2018) Calcium signaling and cell cycle: progression or death. Cell Calcium 70:3–15. https://doi.org/10.1016/j.ceca.2017.07.006
Article CAS PubMed Google Scholar
Hwang MS, Schwall CT, Pazarentzos E, Datler C, Alder NN et al (2014) Mitochondrial Ca²⁺ influx targets cardiolipin to disintegrate respiratory chain complex II for cell death induction. Cell Death Differ 21(11):1733–1745. https://doi.org/10.1038/cdd.2014.84
Article CAS PubMed PubMed Central Google Scholar
Ivanova H, Vervliet T, Missiaen L, Parys JB, De Smedt H et al (2014) Inositol 1,4,5-trisphosphate receptor-isoform diversity in cell death and survival. Biochim Biophys Acta 1843(10):2164–2183. https://doi.org/10.1016/j.bbamcr.2014.03.007
Article CAS PubMed Google Scholar
Ivanova H, Vervliet T, Monaco G, Terry LE, Rosa N et al (2020) Bcl-2-protein family as modulators of IP₃ receptors and other organellar Ca²⁺ channels. Cold Spring Harb Perspect Biol 12(4):a035089. https://doi.org/10.1101/cshperspect.a035089
Article CAS PubMed PubMed Central Google Scholar
Iwai M, Michikawa T, Bosanac I, Ikura M, Mikoshiba K (2007) Molecular basis of the isoform-specific ligand-binding affinity of inositol 1,4,5-trisphosphate receptors. J Biol Chem 282(17):12755–12764. https://doi.org/10.1074/jbc.M609833200
Article CAS PubMed Google Scholar
Kale J, Osterlund EJ, Andrews DW (2018) BCL-2 family proteins: changing partners in the dance towards death. Cell Death Differ 25(1):65–80. https://doi.org/10.1038/cdd.2017.186
Article CAS PubMed Google Scholar
Kania E, Roest G, Vervliet T, Parys JB, Bultynck G (2017) IP₃ receptor-mediated calcium signaling and its role in autophagy in cancer. Front Oncol 7:140. https://doi.org/10.3389/fonc.2017.00140
Article PubMed PubMed Central Google Scholar
Kerkhofs M, Seitaj B, Ivanova H, Monaco G, Bultynck G et al (2018) Pathophysiological consequences of isoform-specific IP₃ receptor mutations. Biochim Biophys Acta Mol Cell Res 1865(11 Pt B):1707–1717. https://doi.org/10.1016/j.bbamcr.2018.06.004
Article CAS PubMed Google Scholar
Kilpatrick BS, Eden ER, Schapira AH, Futter CE, Patel S (2013) Direct mobilisation of lysosomal Ca²⁺ triggers complex Ca²⁺ signals. J Cell Sci 126(Pt 1):60–66. https://doi.org/10.1242/jcs.118836
Article CAS PubMed Google Scholar
La Rovere RM, Roest G, Bultynck G, Parys JB (2016) Intracellular Ca²⁺ signaling and Ca²⁺ microdomains in the control of cell survival, apoptosis and autophagy. Cell Calcium 60(2):74–87. https://doi.org/10.1016/j.ceca.2016.04.005
Article CAS PubMed Google Scholar
Lam D, Kosta A, Luciani MF, Golstein P (2008) The inositol 1,4,5-trisphosphate receptor is required to signal autophagic cell death. Mol Biol Cell 19(2):691–700. https://doi.org/10.1091/mbc.e07-08-0823
Article CAS PubMed PubMed Central Google Scholar
Lavik AR, Zhong F, Chang MJ, Greenberg E, Choudhary Y et al (2015) A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2. Oncotarget 6(29):27388–27402. https://doi.org/10.18632/oncotarget.4489
Article PubMed PubMed Central Google Scholar
Lewis RS (2020) Store-operated calcium channels: from function to structure and back again. Cold Spring Harb Perspect Biol 12(5):a035055. https://doi.org/10.1101/cshperspect.a035055
Article CAS PubMed PubMed Central Google Scholar
Liu EY, Ryan KM (2012) Autophagy and cancer--issues we need to digest. J Cell Sci 125(Pt 10):2349–2358. https://doi.org/10.1242/jcs.093708
Article CAS PubMed Google Scholar
Liu AJ, Wang SH, Chen KC, Kuei HP, Shih YL et al (2013) Evodiamine, a plant alkaloid, induces calcium/JNK-mediated autophagy and calcium/mitochondria-mediated apoptosis in human glioblastoma cells. Chem Biol Interact 205(1):20–28. https://doi.org/10.1016/j.cbi.2013.06.004
Article CAS PubMed Google Scholar
Lock JT, Smith IF, Parker I (2019) Spatial-temporal patterning of Ca²⁺ signals by the subcellular distribution of IP₃ and IP₃ receptors. Semin Cell Dev Biol 94:3–10. https://doi.org/10.1016/j.semcdb.2019.01.012
Article CAS PubMed PubMed Central Google Scholar
Lopez-Sanjurjo CI, Tovey SC, Prole DL, Taylor CW (2013) Lysosomes shape Ins(1,4,5)P₃-evoked Ca²⁺ signals by selectively sequestering Ca²⁺ released from the endoplasmic reticulum. J Cell Sci 126(Pt 1):289–300. https://doi.org/10.1242/jcs.116103
Luyten T, Welkenhuyzen K, Roest G, Kania E, Wang L et al (2017) Resveratrol-induced autophagy is dependent on IP₃Rs and on cytosolic Ca²⁺. Biochim Biophys Acta, Mol Cell Res 1864(6):947–956. https://doi.org/10.1016/j.bbamcr.2017.02.013
Article CAS Google Scholar
Mendes CC, Gomes DA, Thompson M, Souto NC, Goes TS et al (2005) The type III inositol 1,4,5-trisphosphate receptor preferentially transmits apoptotic Ca²⁺ signals into mitochondria. J Biol Chem 280(49):40892–40900. https://doi.org/10.1074/jbc.M506623200
Article CAS PubMed Google Scholar
Messai Y, Noman MZ, Hasmim M, Janji B, Tittarelli A et al (2014) ITPR1 protects renal cancer cells against natural killer cells by inducing autophagy. Cancer Res 74(23):6820–6832. https://doi.org/10.1158/0008-5472.CAN-14-0303
Article CAS PubMed Google Scholar
Monteith GR, Prevarskaya N, Roberts-Thomson SJ (2017) The calcium-cancer signalling nexus. Nat Rev Cancer 17(6):367–380. https://doi.org/10.1038/nrc.2017.18
Article CAS PubMed Google Scholar
Morciano G, Marchi S, Morganti C, Sbano L, Bittremieux M et al (2018) Role of mitochondria-associated ER membranes in calcium regulation in cancer-specific settings. Neoplasia 20(5):510–523. https://doi.org/10.1016/j.neo.2018.03.005
Article CAS PubMed PubMed Central Google Scholar
Morgan AJ, Davis LC, Wagner SK, Lewis AM, Parrington J et al (2013) Bidirectional Ca²⁺ signaling occurs between the endoplasmic reticulum and acidic organelles. J Cell Biol 200(6):789–805. https://doi.org/10.1083/jcb.201204078
Article CAS PubMed PubMed Central Google Scholar
Mound A, Rodat-Despoix L, Bougarn S, Ouadid-Ahidouch H, Matifat F (2013) Molecular interaction and functional coupling between type 3 inositol 1,4,5-trisphosphate receptor and BK_Ca channel stimulate breast cancer cell proliferation. Eur J Cancer 49(17):3738–3751. https://doi.org/10.1016/j.ejca.2013.07.013
Mound A, Vautrin-Glabik A, Foulon A, Botia B, Hague F et al (2017) Downregulation of type 3 inositol (1,4,5)-trisphosphate receptor decreases breast cancer cell migration through an oscillatory Ca²⁺ signal. Oncotarget 8(42):72324–72341. https://doi.org/10.18632/oncotarget.20327
Article PubMed PubMed Central Google Scholar
Okeke E, Parker T, Dingsdale H, Concannon M, Awais M et al (2016) Epithelial-mesenchymal transition, IP₃ receptors and ER-PM junctions: translocation of Ca²⁺ signalling complexes and regulation of migration. Biochem J 473(6):757–767. https://doi.org/10.1042/BJ20150364
Article CAS PubMed Google Scholar
Paknejad N, Hite RK (2018) Structural basis for the regulation of inositol trisphosphate receptors by Ca²⁺ and IP₃. Nat Struct Mol Biol 25(8):660–668. https://doi.org/10.1038/s41594-018-0089-6
Article CAS PubMed PubMed Central Google Scholar
Parys JB, De Smedt H (2012) Inositol 1,4,5-trisphosphate and its receptors. Adv Exp Med Biol 740:255–279. https://doi.org/10.1007/978-94-007-2888-2_11
Article CAS PubMed Google Scholar
Parys JB, Vervliet T (2020) New insights in the IP₃ receptor and its regulation. Adv Exp Med Biol 1131:243–270. https://doi.org/10.1007/978-3-030-12457-1_10
Article CAS PubMed Google Scholar
Parys JB, Decuypere JP, Bultynck G (2012) Role of the inositol 1,4,5-trisphosphate receptor/Ca²⁺-release channel in autophagy. Cell Commun Signal 10(1):17. https://doi.org/10.1186/1478-811X-10-17
Article CAS PubMed PubMed Central Google Scholar
Pierro C, Cook SJ, Foets TC, Bootman MD, Roderick HL (2014) Oncogenic K-Ras suppresses IP₃-dependent Ca²⁺ release through remodelling of the isoform composition of IP₃Rs and ER luminal Ca²⁺ levels in colorectal cancer cell lines. J Cell Sci 127(Pt 7):1607–1619. https://doi.org/10.1242/jcs.141408
Article CAS PubMed Google Scholar
Pierro C, Zhang X, Kankeu C, Trebak M, Bootman MD et al (2018) Oncogenic KRAS suppresses store-operated Ca²⁺ entry and I_CRAC through ERK pathway-dependent remodelling of STIM expression in colorectal cancer cell lines. Cell Calcium 72:70–80. https://doi.org/10.1016/j.ceca.2018.03.002
Pierro C, Sneyers F, Bultynck G, Roderick HL (2019) ER Ca²⁺ release and store-operated Ca²⁺ entry - partners in crime or independent actors in oncogenic transformation? Cell Calcium 82:102061. https://doi.org/10.1016/j.ceca.2019.102061
Article CAS PubMed Google Scholar
Prevarskaya N, Skryma R, Shuba Y (2018) Ion channels in cancer: are cancer hallmarks oncochannelopathies? Physiol Rev 98(2):559–621. https://doi.org/10.1152/physrev.00044.2016
Article CAS PubMed Google Scholar
Prole DL, Taylor CW (2016) Inositol 1,4,5-trisphosphate receptors and their protein partners as signalling hubs. J Physiol 594(11):2849–2866. https://doi.org/10.1113/JP271139
Article CAS PubMed PubMed Central Google Scholar
Prole DL, Taylor CW (2019) Structure and function of IP₃ receptors. Cold Spring Harb Perspect Biol 11(4):a035063. https://doi.org/10.1101/cshperspect.a035063
Article CAS PubMed PubMed Central Google Scholar
Ravikumar B, Sarkar S, Davies JE, Futter M, Garcia-Arencibia M et al (2010) Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev 90(4):1383–1435. https://doi.org/10.1152/physrev.00030.2009
Article CAS PubMed Google Scholar
Rezuchova I, Hudecova S, Soltysova A, Matuskova M, Durinikova E et al (2019) Type 3 inositol 1,4,5-trisphosphate receptor has antiapoptotic and proliferative role in cancer cells. Cell Death Dis 10(3):186. https://doi.org/10.1038/s41419-019-1433-4
Article CAS PubMed PubMed Central Google Scholar
Rizzuto R, Brini M, Murgia M, Pozzan T (1993) Microdomains with high Ca²⁺ close to IP₃-sensitive channels that are sensed by neighboring mitochondria. Science 262(5134):744–747. https://doi.org/10.1126/science.8235595
Article CAS PubMed Google Scholar
Roberts-Thomson SJ, Chalmers SB, Monteith GR (2019) The calcium-signaling toolkit in cancer: remodeling and targeting. Cold Spring Harb Perspect Biol 11(8):a035204. https://doi.org/10.1101/cshperspect.a035204
Article CAS PubMed PubMed Central Google Scholar
Roderick HL, Cook SJ (2008) Ca²⁺ signalling checkpoints in cancer: remodelling Ca²⁺ for cancer cell proliferation and survival. Nat Rev Cancer 8(5):361–375. https://doi.org/10.1038/nrc2374
Article CAS PubMed Google Scholar
Rong YP, Aromolaran AS, Bultynck G, Zhong F, Li X et al (2008) Targeting Bcl-2-IP₃ receptor interaction to reverse Bcl-2’s inhibition of apoptotic calcium signals. Mol Cell 31(2):255–265. https://doi.org/10.1016/j.molcel.2008.06.014
Article CAS PubMed PubMed Central Google Scholar
Rosa N, Sneyers F, Parys JB, Bultynck G (2020) Type 3 IP₃ receptors: the chameleon in cancer. Int Rev Cell Mol Biol 351:101–148. https://doi.org/10.1016/bs.ircmb.2020.02.003
Article PubMed Google Scholar
Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F et al (1998) Two CD95 (APO-1/Fas) signaling pathways. EMBO J 17(6):1675–1687. https://doi.org/10.1093/emboj/17.6.1675
Article CAS PubMed PubMed Central Google Scholar
Serysheva II, Baker MR, Fan G (2017) Structural insights into IP₃R function. Adv Exp Med Biol 981:121–147. https://doi.org/10.1007/978-3-319-55858-5_6
Article CAS PubMed Google Scholar
Shibao K, Fiedler MJ, Nagata J, Minagawa N, Hirata K et al (2010) The type III inositol 1,4,5-trisphosphate receptor is associated with aggressiveness of colorectal carcinoma. Cell Calcium 48(6):315–323. https://doi.org/10.1016/j.ceca.2010.09.005
Article CAS PubMed PubMed Central Google Scholar
Singh A, Chagtoo M, Tiwari S, George N, Chakravarti B et al (2017a) Inhibition of inositol 1, 4, 5-trisphosphate receptor induce breast cancer cell death through deregulated autophagy and cellular bioenergetics. J Cell Biochem 118(8):2333–2346. https://doi.org/10.1002/jcb.25891
Article CAS PubMed Google Scholar
Singh A, Sharma RK, Chagtoo M, Agarwal G, George N et al (2017b) ¹H NMR metabolomics reveals association of high expression of inositol 1, 4, 5 trisphosphate receptor and metabolites in breast cancer patients. PLoS One 12(1):e0169330. https://doi.org/10.1371/journal.pone.0169330
Singh R, Letai A, Sarosiek K (2019) Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol 20(3):175–193. https://doi.org/10.1038/s41580-018-0089-8
Article CAS PubMed PubMed Central Google Scholar
Smaili SS, Pereira GJ, Costa MM, Rocha KK, Rodrigues L et al (2013) The role of calcium stores in apoptosis and autophagy. Curr Mol Med 13(2):252–265. https://doi.org/10.2174/156652413804810772
Article CAS PubMed Google Scholar
Steinmann C, Landsverk ML, Barral JM, Boehning D (2008) Requirement of inositol 1,4,5-trisphosphate receptors for tumor-mediated lymphocyte apoptosis. J Biol Chem 283(20):13506–13509. https://doi.org/10.1074/jbc.C800029200
Article CAS PubMed PubMed Central Google Scholar
Südhof TC, Newton CL, Archer BT 3^rd, Ushkaryov YA, Mignery GA (1991) Structure of a novel InsP₃ receptor. EMBO J 10(11):3199–3206
Google Scholar
Sun F, Xu X, Wang X, Zhang B (2016) Regulation of autophagy by Ca²⁺. Tumour Biol 37:15467–15476. https://doi.org/10.1007/s13277-016-5353-y
Article CAS Google Scholar
Sung PJ, Tsai FD, Vais H, Court H, Yang J et al (2013) Phosphorylated K-Ras limits cell survival by blocking Bcl-xL sensitization of inositol trisphosphate receptors. Proc Natl Acad Sci U S A 110(51):20593–20598. https://doi.org/10.1073/pnas.1306431110
Article CAS PubMed PubMed Central Google Scholar
Szabadkai G, Bianchi K, Varnai P, De Stefani D, Wieckowski MR et al (2006) Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca²⁺ channels. J Cell Biol 175(6):901–911. https://doi.org/10.1083/jcb.200608073
Article CAS PubMed PubMed Central Google Scholar
Szatkowski C, Parys JB, Ouadid-Ahidouch H, Matifat F (2010) Inositol 1,4,5-trisphosphate-induced Ca²⁺ signalling is involved in estradiol-induced breast cancer epithelial cell growth. Mol Cancer 9:156. https://doi.org/10.1186/1476-4598-9-156
Article CAS PubMed PubMed Central Google Scholar
Taylor CW, Tovey SC (2010) IP₃ receptors: toward understanding their activation. Cold Spring Harb Perspect Biol 2(12):a004010. https://doi.org/10.1101/cshperspect.a004010
Article CAS PubMed PubMed Central Google Scholar
Taylor CW, da Fonseca PC, Morris EP (2004) IP₃ receptors: the search for structure. Trends Biochem Sci 29(4):210–219. https://doi.org/10.1016/j.tibs.2004.02.010
Article CAS PubMed Google Scholar
Terry LE, Alzayady KJ, Furati E, Yule DI (2018) Inositol 1,4,5-trisphosphate receptor mutations associated with human disease. Messenger (Los Angel) 6(1–2):29–44
Google Scholar
Thillaiappan NB, Chavda AP, Tovey SC, Prole DL, Taylor CW (2017) Ca²⁺ signals initiate at immobile IP₃ receptors adjacent to ER-plasma membrane junctions. Nat Commun 8(1):1505. https://doi.org/10.1038/s41467-017-01644-8
Article CAS PubMed PubMed Central Google Scholar
Ueasilamongkol P, Khamphaya T, Guerra MT, Rodrigues MA, Gomes DA et al (2020) Type 3 inositol 1,4,5-trisphosphate receptor is increased and enhances malignant properties in cholangiocarcinoma. Hepatology 71(2):583–599. https://doi.org/10.1002/hep.30839
Article CAS PubMed Google Scholar
Urbani A, Giorgio V, Carrer A, Franchin C, Arrigoni G et al (2019) Purified F-ATP synthase forms a Ca²⁺-dependent high-conductance channel matching the mitochondrial permeability transition pore. Nat Commun 10(1):4341. https://doi.org/10.1038/s41467-019-12331-1
Article CAS PubMed PubMed Central Google Scholar
Vanderheyden V, Devogelaere B, Missiaen L, De Smedt H, Bultynck G et al (2009) Regulation of inositol 1,4,5-trisphosphate-induced Ca²⁺ release by reversible phosphorylation and dephosphorylation. Biochim Biophys Acta 1793(6):959–970. https://doi.org/10.1016/j.bbamcr.2008.12.003
Article CAS PubMed Google Scholar
Vautrin-Glabik A, Botia B, Kischel P, Ouadid-Ahidouch H, Rodat-Despoix L (2018) IP₃R3 silencing induced actin cytoskeletal reorganization through ARHGAP18/RhoA/mDia1/FAK pathway in breast cancer cell lines. Biochim Biophys Acta, Mol Cell Res 1865(7):945–958. https://doi.org/10.1016/j.bbamcr.2018.04.002
Article CAS Google Scholar
Vermassen E, Parys JB, Mauger JP (2004) Subcellular distribution of the inositol 1,4,5-trisphosphate receptors: functional relevance and molecular determinants. Biol Cell 96(1):3–17. https://doi.org/10.1016/j.biolcel.2003.11.004
Article CAS PubMed Google Scholar
Vervloessem T, Yule DI, Bultynck G, Parys JB (2015) The type 2 inositol 1,4,5-trisphosphate receptor, emerging functions for an intriguing Ca²⁺-release channel. Biochim Biophys Acta 1853(9):1992–2005. https://doi.org/10.1016/j.bbamcr.2014.12.006
Article CAS PubMed Google Scholar
Vervloessem T, Akl H, Tousseyn T, De Smedt H, Parys JB et al (2017) Reciprocal sensitivity of diffuse large B-cell lymphoma cells to Bcl-2 inhibitors BIRD-2 versus venetoclax. Oncotarget 8(67):111656–111671. https://doi.org/10.18632/oncotarget.22898
Article PubMed PubMed Central Google Scholar
Wang SH, Shih YL, Ko WC, Wei YH, Shih CM (2008) Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway. Cell Mol Life Sci 65(22):3640–3652. https://doi.org/10.1007/s00018-008-8383-9
Article CAS PubMed Google Scholar
White C, Li C, Yang J, Petrenko NB, Madesh M et al (2005) The endoplasmic reticulum gateway to apoptosis by Bcl-X_L modulation of the InsP₃R. Nat Cell Biol 7(10):1021–1028. https://doi.org/10.1038/ncb1302
Wozniak AL, Wang X, Stieren ES, Scarbrough SG, Elferink CJ et al (2006) Requirement of biphasic calcium release from the endoplasmic reticulum for Fas-mediated apoptosis. J Cell Biol 175(5):709–714. https://doi.org/10.1083/jcb.200608035
Article CAS PubMed PubMed Central Google Scholar
Xie Q, Xu Y, Gao W, Zhang Y, Su J et al (2018) TAT-fused IP₃R-derived peptide enhances cisplatin sensitivity of ovarian cancer cells by increasing ER Ca²⁺ release. Int J Mol Med 41(2):809–817. https://doi.org/10.3892/ijmm.2017.3260
Yue Z, Jin S, Yang C, Levine AJ, Heintz N (2003) Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci U S A 100(25):15077–15082. https://doi.org/10.1073/pnas.2436255100
Article CAS PubMed PubMed Central Google Scholar
Zhong F, Harr MW, Bultynck G, Monaco G, Parys JB et al (2011) Induction of Ca²⁺-driven apoptosis in chronic lymphocytic leukemia cells by peptide-mediated disruption of Bcl-2-IP₃ receptor interaction. Blood 117(10):2924–2934. https://doi.org/10.1182/blood-2010-09-307405
Article CAS PubMed PubMed Central Google Scholar
Zhou Y, Nwokonko RM, Baraniak JH Jr, Trebak M, Lee KPK et al (2019) The remote allosteric control of Orai channel gating. PLoS Biol 17(8):e3000413. https://doi.org/10.1371/journal.pbio.3000413
Article CAS PubMed PubMed Central Google Scholar

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Acknowledgements

Research work performed in our laboratory on this topic was supported by grants from the Research Foundation—Flanders (FWO) (G073109N, G057112N, G081913N, G063413N, G0C9114N, G092715N, G0A3416N, G090118N and G0A6919N), the Inter University Attraction Poles program P7/13 and by the Research Council of the KU Leuven (Concerted Actions G.O.A. 09/012 and grants 14/101 and C14/19/099). T.V. obtained a postdoctoral fellowship of the FWO. G.B. and J.B.P. are part of the FWO Scientific Research Network CaSign (W0.019.17N).

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Laboratory for Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine & Leuven Cancer Institute, KU Leuven, Leuven, Belgium
Jan B. Parys, Geert Bultynck & Tim Vervliet

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Jan B. Parys
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School of Human Nutrition, McGill University, Ste. Anne de Bellevue, QC, Canada
Luis B. Agellon
Department of Biochemistry, University of Alberta, Edmonton, AB, Canada
Marek Michalak

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Parys, J.B., Bultynck, G., Vervliet, T. (2021). IP₃ Receptor Biology and Endoplasmic Reticulum Calcium Dynamics in Cancer. In: Agellon, L.B., Michalak, M. (eds) Cellular Biology of the Endoplasmic Reticulum . Progress in Molecular and Subcellular Biology, vol 59. Springer, Cham. https://doi.org/10.1007/978-3-030-67696-4_11

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IP3 Receptor Biology and Endoplasmic Reticulum Calcium Dynamics in Cancer