Endoplasmic reticulum stress–activated cell reprogramming in oncogenesis

Cancer Discovery

Volumn 5, Issue 6, 2015, Pages 586-597

  Chevet, Eric ^a,b   Hetz, Claudio ^c,d,e   Samali, Afshin ^f  

^a UNIVERSITÉ DE RENNES 1   (France)

^b Nuclear Medicine Department   (France)

^c UNIVERSITY OF CHILE   (Chile)

^d UNIVERSITY OF CHILE   (Chile)

^e HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^f NATIONAL UNIVERSITY OF IRELAND   (Ireland)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 6; APOPTOSIS SIGNAL REGULATING KINASE 1; CAMP RESPONSIVE ELEMENT BINDING PROTEIN 3 LIKE 2; CRYOPYRIN; DIACYLGLYCEROL; GLUCOSE TRANSPORTER 1; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INITIATION FACTOR 2ALPHA; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE KINASE 4; PROTEIN IRE1; PROTEIN KINASE R LIKE ENDOPLASMIC RETICULUM KINASE; PROTEIN NOXA; PUMA PROTEIN; THIOREDOXIN INTERACTING PROTEIN; TRANSCRIPTION FACTOR FKHR; TRANSCRIPTION FACTOR FOXO; UNCLASSIFIED DRUG; X BOX BINDING PROTEIN 1;

CANCER CELL; CARCINOGENESIS; CELL TRANSFORMATION; CROSS RESISTANCE; DNA DAMAGE; DNA REPAIR; DNA TRANSCRIPTION; ENDOPLASMIC RETICULUM STRESS; GENE EXPRESSION; HUMAN; INTRACELLULAR SIGNALING; METABOLISM; NONHUMAN; NUCLEAR REPROGRAMMING; PROTEIN FOLDING; REVIEW; RNA SPLICING; RNA STABILITY; TRANSFORMED CELL; TUMOR GENE; TUMOR GROWTH; TUMOR MICROENVIRONMENT; UNFOLDED PROTEIN RESPONSE; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORK; GENETIC TRANSCRIPTION; GENETICS; NEOPLASM; RNA PROCESSING; SIGNAL TRANSDUCTION;

CELL TRANSFORMATION, NEOPLASTIC; CELLULAR REPROGRAMMING; ENDOPLASMIC RETICULUM STRESS; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE REGULATORY NETWORKS; HUMANS; NEOPLASMS; RNA PROCESSING, POST-TRANSCRIPTIONAL; SIGNAL TRANSDUCTION; TRANSCRIPTION, GENETIC; UNFOLDED PROTEIN RESPONSE;

EID: 84975796689     PISSN: 21598274     EISSN: 21598290     Source Type: Journal    
DOI: 10.1158/2159-8290.CD-14-1490     Document Type: Review

References (154)

1. Kozutsumi Y, Segal M, Normington K, Gething MJ, Sambrook J. The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature 1988; 332: 462–4.
2. Cox JS, Walter P. A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell 1996; 87: 391–404.
3. Shi Y, Vattem KM, Sood R, An J, Liang J, Stramm L, et al. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Mol Cell Biol 1998; 18: 7499–509.
4. Haze K, Yoshida H, Yanagi H, Yura T, Mori K. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell 1999; 10: 3787–99.
5. Mori K, Ma W, Gething MJ, Sambrook J. A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus. Cell 1993; 74: 743–56.
6. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2000; 2: 326–32.
7. Shen J, Chen X, Hendershot L, Prywes R. ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev Cell 2002; 3: 99–111.
8. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 2007; 8: 519–29.
9. Blais JD, Filipenko V, Bi M, Harding HP, Ron D, Koumenis C, et al. Activating transcription factor 4 is translationally regulated by hypoxic stress. Mol Cell Biol 2004; 24: 7469–82.
10. Ye J, Koumenis C. ATF4, an ER stress and hypoxia-inducible transcription factor and its potential role in hypoxia tolerance and tumorigenesis. Curr Mol Med 2009; 9: 411–6.
11. Zinszner H, Kuroda M, Wang X, Batchvarova N, Lightfoot RT, Remotti H, et al. CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev 1998; 12: 982–95.
12. Novoa I, Zeng H, Harding HP, Ron D. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J Cell Biol 2001; 153: 1011–22.
13. Del Vecchio CA, Feng Y, Sokol ES, Tillman EJ, Sanduja S, Reinhardt F, et al. De-differentiation confers multidrug resistance via noncanonical PERK-Nrf2 signaling. PLoS Biol 2014; 12: e1001945.
14. Cullinan SB, Zhang D, Hannink M, Arvisais E, Kaufman RJ, Diehl JA. Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol Cell Biol 2003; 23: 7198–209.
15. Cullinan SB, Diehl JA. PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J Biol Chem 2004; 279: 20108–17.
16. Zhang W, Hietakangas V, Wee S, Lim SC, Gunaratne J, Cohen S M. ER stress potentiates insulin resistance through PERK-mediated FOXO phosphorylation. Genes Dev 2013; 27: 441–9.
17. Bobrovnikova-Marjon E, Pytel D, Riese MJ, Vaites LP, Singh N, Koretzky GA, et al. PERK utilizes intrinsic lipid kinase activity to generate phosphatidic acid, mediate Akt activation, and promote adipocyte differentiation. Mol Cell Biol 2012; 32: 2268–78.
18. Axten JM, Medina JR, Feng Y, Shu A, Romeril SP, Grant SW, et al. Discovery of 7-methyl-5-(1-{[3-(trifl uoromethyl)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 2012; 55: 7193–207.
19. Atkins C, Liu Q, Minthorn EA, Zhang S, Figueroa DJ, Moss KG, et al. Characterization of a novel PERK kinase inhibitor with anti-tumor and anti-angiogenic activity. Cancer Res 2013; 73: 1993–2002.
20. Shen J, Prywes R. 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 2004; 279: 43046–51.
21. Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, et al. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell 2000; 6: 1355–64.
22. Nadanaka S, Okada T, Yoshida H, Mori K. Role of disulfide bridges formed in the luminal domain of ATF6 in sensing endoplasmic reticulum stress. Mol Cell Biol 2007; 27: 1027–43.
23. Higa A, Taouji S, Lhomond S, Jensen D, Fernandez-Zapico ME, Simpson JC, et al. Endoplasmic reticulum stress-activated transcription factor ATF6alpha requires the disulfide isomerase PDIA5 to modulate chemoresistance. Mol Cell Biol 2014; 34: 1839–49.
24. Yamamoto K, Sato T, Matsui T, Sato M, Okada T, Yoshida H, et al. Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1. Dev Cell 2007; 13: 365–76.
25. Yoshida H, Okada T, Haze K, Yanagi H, Yura T, Negishi M, et al. 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 2000; 20: 6755–67.
26. Asada R, Kanemoto S, Kondo S, Saito A, Imaizumi K. The signalling from endoplasmic reticulum-resident bZIP transcription factors involved in diverse cellular physiology. J Biochem 2011; 149: 507–18.
27. Hino K, Saito A, Kido M, Kanemoto S, Asada R, Takai T, et al. Master regulator for chondrogenesis, Sox9, regulates transcriptional activation of the endoplasmic reticulum stress transducer BBF2H7/ CREB3L2 in chondrocytes. J Biol Chem 2014; 289: 13810–20.
28. Saito A, Kanemoto S, Zhang Y, Asada R, Hino K, Imaizumi K. Chondrocyte proliferation regulated by secreted luminal domain of ER stress transducer BBF2H7/CREB3L2. Mol Cell 2013; 53: 127–39.
29. Adachi Y, Yamamoto K, Okada T, Yoshida H, Harada A, Mori K. ATF6 is a transcription factor specializing in the regulation of quality control proteins in the endoplasmic reticulum. Cell Struct Funct 2008; 33: 75–89.
30. Schewe DM, Aguirre-Ghiso JA. ATF6alpha-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivo. Proc Natl Acad Sci U S A 2008; 105: 10519–24.
31. Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 2002; 415: 92–6.
32. Shen X, Ellis RE, Lee K, Liu CY, Yang K, Solomon A, e t al. Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development. Cell 2001; 107: 893–903.
33. Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 2001; 107: 881–91.
34. Lee K, Tirasophon W, Shen X, Michalak M, Prywes R, Okada T, et al. IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev 2002; 16: 452–66.
35. Maurel M, Chevet E, Tavernier J, Gerlo S. Getting RIDD of RNA: IRE1 in cell fate regulation. Trends Biochem Sci 2014; 39: 245–54.
36. Hollien J, Lin JH, Li H, Stevens N, Walter P, Weissman JS. Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J Cell Biol 2009; 186: 323–31.
37. Hollien J, Weissman JS. Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science 2006; 313: 104–7.
38. Iwawaki T, Hosoda A, Okuda T, Kamigori Y, Nomura-Furuwatari C, Kimata Y, et al. Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress. Nat Cell Biol 2001; 3: 158–64.
39. Lerner AG, Upton JP, Praveen PV, Ghosh R, Nakagawa Y, Igbaria A, et al. IRE1alpha induces thioredoxin-interacting protein to activate the NLRP3 infl ammasome and promote programmed cell death under irremediable ER stress. Cell Metab 2012; 16: 250–64.
40. Upton JP, Wang L, Han D, Wang ES, Huskey NE, Lim L, e t al. IRE1alpha cleaves select microRNAs during ER stress to derepress translation of proapoptotic caspase-2. Science 2012; 338: 818–22.
41. Hetz C, Martinon F, Rodriguez D, Glimcher LH. The unfolded protein response: integrating stress signals through the stress sensor IRE1alpha. Physiol Rev 2011; 91: 1219–43.
42. Shoulders MD, Ryno LM, Genereux JC, Moresco JJ, Tu PG, Wu C, et al. Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments. Cell Rep 2013; 3: 1279–92.
43. Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 2012; 13: 89–102.
44. Tam AB, Koong AC, Niwa M. Ire1 has distinct catalytic mechanisms for XBP1/HAC1 splicing and RIDD. Cell Rep 2014; 9: 1–9.
45. Bouchecareilh M, Higa A, Fribourg S, Moenner M, Chevet E. Peptides derived from the bifunctional kinase/RNase enzyme IRE1{alpha} modulate IRE1{alpha} activity and protect cells from endoplasmic reticulum stress. FASEB J 2011; 25: 3115–29.
46. Prischi F, Nowak PR, Carrara M, Ali MM. Phosphoregulation of Ire1 RNase splicing activity. Nat Commun 2014; 5: 3554.
47. Rubio C, Pincus D, Korennykh A, Schuck S, El-Samad H, Walter P. Homeostatic adaptation to endoplasmic reticulum stress depends on Ire1 kinase activity. J Cell Biol 2011; 193: 171–84.
48. Chawla A, Chakrabarti S, Ghosh G, Niwa M. Attenuation of yeast UPR is essential for survival and is mediated by IRE1 kinase. J Cell Biol 2011; 193: 41–50.
49. Jurkin J, Henkel T, Nielsen AF, Minnich M, Popow J, Kaufmann T, et al. The mammalian tRNA ligase complex mediates splicing of XBP1 mRNA and controls antibody secretion in plasma cells. EMBO J 2014; 33: 2922–36.
50. Kosmaczewski SG, Edwards TJ, Han SM, Eckwahl MJ, Meyer BI, Peach S, et al. The RtcB RNA ligase is an essential component of the metazoan unfolded protein response. EMBO Rep 2014; 15: 1278–85.
51. Lu Y, Liang FX, Wang X. A synthetic biology approach identifies the mammalian UPR RNA ligase RtcB. Mol Cell 2014; 55: 758–70.
52. Ray A, Zhang S, Rentas C, Caldwell KA, Caldwell GA. RTCB-1 mediates neuroprotection via XBP-1 mRNA splicing in the unfolded protein response pathway. J Neurosci 2014; 34: 16076–85.
53. Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP, et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 2000; 287: 664–6.
54. Ma Y, Hendershot LM. The role of the unfolded protein response in tumour development: friend or foe? Nat Rev Cancer 2004; 4: 966–77.
55. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, et al. Patterns of somatic mutation in human cancer genomes. Nature 2007; 446: 153–8.
56. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321: 1807–12.
57. Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, et al. Integrated analysis of somatic mutations and focal copynumber changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet 2012; 44: 694–8.
58. Forbes SA, Tang G, Bindal N, Bamford S, Dawson E, Cole C, et al. COSMIC (the Catalogue of Somatic Mutations in Cancer): a resource to investigate acquired mutations in human cancer. Nucleic Acids Res 2009; 38: D652–7.
59. Xue Z, He Y, Ye K, Gu Z, Mao Y, Qi L. A conserved structural determinant located at the interdomain region of mammalian inositolrequiring enzyme 1alpha. J Biol Chem 2011; 286: 30859–66.
60. Pluquet O, Dejeans N, Bouchecareilh M, Lhomond S, Pineau R, Higa A, et al. Posttranscriptional regulation of PER1 underlies the oncogenic function of IREalpha. Cancer Res 2013; 73: 4732–43.
61. Hart LS, Cunningham JT, Datta T, Dey S, Tameire F, Lehman SL, et al. ER stress–mediated autophagy promotes Myc-dependent transformation and tumor growth. J Clin Invest 2012; 122: 4621–34.
62. Nagy P, Varga A, Pircs K, Hegedus K, Juhasz G. Myc-driven overgrowth requires unfolded protein response-mediated induction of autophagy and antioxidant responses in Drosophila melanogaster. PLoS Genet 2013; 9: e1003664.
63. Chen X, Iliopoulos D, Zhang Q, Tang Q, Greenblatt MB, Hatziapostolou M, et al. XBP1 promotes triple-negative breast cancer by controlling the HIF1alpha pathway. Nature 2014; 508: 103–7.
64. Cornejo VH, Hetz C. The unfolded protein response in Alzheimer’s disease. Semin Immunopathol 2013; 35: 277–92.
65. Lee A-H, Iwakoshi NN, Glimcher LH. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol 2003; 23: 7448–59.
66. Acosta-Alvear D, Zhou Y, Blais A, Tsikitis M, Lents NH, Arias C, et al. XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Mol Cell 2007; 27: 53–66.
67. Harding HP, Zhang Y, Zeng H, Novoa I, Lu PD, Calfon M, et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell 2003; 11: 619–33.
68. Shaffer AL, Shapiro-Shelef M, Iwakoshi NN, Lee AH, Qian SB, Zhao H, et al. XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity 2004; 21: 81–93.
69. Luo R, Lu JF, Hu Q, Maity SN. CBF/NF-Y controls endoplasmic reticulum stress induced transcription through recruitment of both ATF6(N) and TBP. J Cell Biochem 2008; 104: 1708–23.
70. Li M, Baumeister P, Roy B, Phan T, Foti D, Luo S, et al. ATF6 as a transcription activator of the endoplasmic reticulum stress element: thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1. Mol Cell Biol 2000; 20: 5096–106.
71. Gade P, Manjegowda SB, Nallar SC, Maachani UB, Cross AS, Kalvakolanu DV. Regulation of the death-associated protein kinase 1 expression and autophagy via ATF6 requires apoptosis signalregulating kinase 1. Mol Cell Biol 2014; 34: 4033–48.
72. Lee J, Sun C, Zhou Y, Gokalp D, Herrema H, Park SW, et al. p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis. Nat Med 2011; 17: 1251–60.
73. Wang FM, Chen YJ, Ouyang HJ. Regulation of unfolded protein response modulator XBP1s by acetylation and deacetylation. Biochem J 2010; 433: 245–52.
74. Chen H, Qi L. SUMO modification regulates the transcriptional activity of XBP1. Biochem J 2010; 429: 95–102.
75. Ameri K, Harris AL. Activating transcription factor 4. Int J Biochem Cell Biol 2008; 40: 14–21.
76. Han J, Back SH, Hur J, Lin YH, Gildersleeve R, Shan J, et al. ERstress- induced transcriptional regulation increases protein synthesis leading to cell death. Nat Cell Biol 2013; 15: 481–90.
77. Huh WJ, Esen E, Geahlen JH, Bredemeyer AJ, Lee AH, Shi G, et al. XBP1 controls maturation of gastric zymogenic cells by induction of MIST1 and expansion of the rough endoplasmic reticulum. Gastroenterology 2010; 139: 2038–49.
78. Hu CC, Dougan SK, McGehee AM, Love JC, Ploegh HL. XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells. EMBO J 2009; 28: 1624–36.
79. Wang M, Kaufman RJ. The impact of the endoplasmic reticulum protein-folding environment on cancer development. Nat Rev Cancer 2014; 14: 581–97.
80. Mujtaba T, Dou QP. Advances in the understanding of mechanisms and therapeutic use of bortezomib. Discov Med 2011; 12: 471–80.
81. Kardosh A, Golden EB, Pyrko P, Uddin J, Hofman FM, Chen TC, et al. Aggravated endoplasmic reticulum stress as a basis for enhanced glioblastoma cell killing by bortezomib in combination with celecoxib or its non-coxib analogue, 2,5-dimethyl-celecoxib. Cancer Res 2008; 68: 843–51.
82. Sidrauski C, McGeachy AM, Ingolia NT, Walter P. The small molecule ISRIB reverses the effects of eIF2alpha phosphorylation on translation and stress granule assembly. Elife 2015; 4: e05033.
83. Halliday M, Radford H, Sekine Y, Moreno J, Verity N, le Quesne J, et al. Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity. Cell Death Dis 2015; 6: e1672.
84. Lee AH, Iwakoshi NN, Anderson KC, Glimcher LH. Proteasome inhibitors disrupt the unfolded protein response in myeloma cells. Proc Natl Acad Sci U S A 2003; 100: 9946–51.
85. Hetz C, Chevet E, Harding HP. Targeting the unfolded protein response in disease. Nat Rev Drug Discov 2013; 12: 703–19.
86. Carrasco DR, Sukhdeo K, Protopopova M, Sinha R, Enos M, Carrasco DE, et al. The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis. Cancer Cell 2007; 11: 349–60.
87. Sengupta S, Sharma CG, Jordan VC. 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 2010; 2: 235–43.
88. Ding L, Yan J, Zhu J, Zhong H, Lu Q, Wang Z, et al. Ligand-independent activation of estrogen receptor alpha by XBP-1. Nucleic Acids Res 2003; 31: 5266–74.
89. Raina K, Noblin DJ, Serebrenik YV, Adams A, Zhao C, Crews CM. Targeted protein destabilization reveals an estrogen-mediated ER stress response. Nat Chem Biol 2014; 10: 957–62.
90. Hu R, Warri A, Jin L, Zwart A, Riggins RB, Clarke R. NFkappaB signaling is required for XBP1 (U and S) mediated effects on antiestrogen responsiveness and cell fate decisions in breast cancer. Mol Cell Biol 2014; 35: 379–90.
91. Gomez BP, Riggins RB, Shajahan AN, Klimach U, Wang A, Crawford AC, et al. Human X-box binding protein-1 confers both estrogen independence and antiestrogen resistance in breast cancer cell lines. FASEB J 2007; 21: 4013–27.
92. Kharabi Masouleh B, Geng H, Hurtz C, Chan LN, Logan AC, Chang MS, et al. Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 2014; 111: E2219–28.
93. Tang CH, Ranatunga S, Kriss CL, Cubitt CL, Tao J, Pinilla-Ibarz JA, et al. Inhibition of ER stress-associated IRE-1/XBP-1 pathway reduces leukemic cell survival. J Clin Invest 2014; 124: 2585–98.
94. Dejeans N, Manie S, Hetz C, Bard F, Hupp T, Agostinis P, et al. Addicted to secrete—novel concepts and targets in cancer therapy. Trends Mol Med 2014; 20: 242–50.
95. Gambella M, Rocci A, Passera R, Gay F, Omede P, Crippa C, et al. High XBP1 expression is a marker of better outcome in multiple myeloma patients treated with bortezomib. Haematologica 2014; 99: e14–6.
96. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 2008; 7: 11–20.
97. Blais JD, Addison CL, Edge R, Falls T, Zhao H, Wary K, et al. Perkdependent translational regulation promotes tumor cell adaptation and angiogenesis in response to hypoxic stress. Mol Cell Biol 2006; 26: 9517–32.
98. Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science 2011; 334: 1081–6.
99. Harding HP, Zhang Y, Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum–resident kinase. Nature 1999; 397: 271–4.
100. Rzymski T, Milani M, Singleton DC, Harris AL. Role of ATF4 in regulation of autophagy and resistance to drugs and hypoxia. Cell Cycle 2009; 8: 3838–47.
101. Deng Y, Wang ZV, Tao C, Gao N, Holland WL, Ferdous A, et al. The Xbp1s/GalE axis links ER stress to postprandial hepatic metabolism. J Clin Invest 2013; 123: 455–68.
102. Wang ZV, Deng Y, Gao N, Pedrozo Z, Li DL, Morales CR, et al. Spliced X-box binding protein 1 couples the unfolded protein response to hexosamine biosynthetic pathway. Cell 2014; 156: 1179–92.
103. Zhou Y, Lee J, Reno CM, Sun C, Park SW, Chung J, et al. Regulation of glucose homeostasis through a XBP-1–FoxO1 interaction. Nat Med 2011; 17: 356–65.
104. Safra M, Fickentscher R, Levi-Ferber M, Danino YM, Haviv-Chesner A, Hansen M, et al. The FOXO transcription factor DAF-16 bypasses ire-1 requirement to promote endoplasmic reticulum homeostasis. Cell Metab 2014; 20: 870–81.
105. Vidal RL, Figueroa A, Court FA, Thielen P, Molina C, Wirth C, et al. Targeting the UPR transcription factor XBP1 protects against Huntington’s disease through the regulation of FoxO1 and autophagy. Hum Mol Genet 2012; 21: 2245–62.
106. Bi M, Naczki C, Koritzinsky M, Fels D, Blais J, Hu N, et al. ER stressregulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J 2005; 24: 3470–81.
107. Rouschop KM, van den Beucken T, Dubois L, Niessen H, Bussink J, Savelkouls K, et al. The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. J Clin Invest 2010; 120: 127–41.
108. Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, et al. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 2006; 26: 9220–31.
109. Robinson KS, Clements A, Williams AC, Berger CN, Frankel G. Bax inhibitor 1 in apoptosis and disease. Oncogene 2011; 30: 2391–400.
110. Rojas-Rivera D, Hetz C. TMBIM protein family: ancestral regulators of cell death. Oncogene 2015; 34: 269–80.
111. Hetz C, Thielen P, Matus S, Nassif M, Court F, Kiffin R, et al. XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev 2009; 23: 2294–306.
112. Yamamori T, Meike S, Nagane M, Yasui H, Inanami O. ER stress suppresses DNA double-strand break repair and sensitizes tumor cells to ionizing radiation by stimulating proteasomal degradation of Rad51. FEBS Lett 2013; 587: 3348–53.
113. Epple LM, Dodd RD, Merz AL, Dechkovskaia AM, Herring M, Winston BA, et al. Induction of the unfolded protein response drives enhanced metabolism and chemoresistance in glioma cells. PLoS One 2013; 8: e73267.
114. Hsu JL, Chiang PC, Guh JH. Tunicamycin induces resistance to camptothecin and etoposide in human hepatocellular carcinoma cells: role of cell-cycle arrest and GRP78. Naunyn Schmiedebergs Arch Pharmacol 2009; 380: 373–82.
115. Al-Rawashdeh FY, Scriven P, Cameron IC, Vergani PV, Wyld L. Unfolded protein response activation contributes to chemoresistance in hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2010; 22: 1099–105.
116. Feng R, Zhai WL, Yang HY, Jin H, Zhang QX. Induction of ER stress protects gastric cancer cells against apoptosis induced by cisplatin and doxorubicin through activation of p38 MAPK. Biochem Biophys Res Commun 2011; 406: 299–304.
117. Strome ED, Wu X, Kimmel M, Plon SE. Heterozygous screen in Saccharomyces cerevisiae identifies dosage-sensitive genes that affect chromosome stability. Genetics 2008; 178: 1193–207.
118. Henry KA, Blank HM, Hoose SA, Polymenis M. The unfolded protein response is not necessary for the G1/S transition, but it is required for chromosome maintenance in Saccharomyces cerevisiae. PLoS One 2010; 5: e12732.
119. He L, Kim SO, Kwon O, Jeong SJ, Kim MS, Lee HG, et al. ATM blocks tunicamycin-induced endoplasmic reticulum stress. FEBS Lett 2009; 583: 903–8.
120. Dioufa N, Chatzistamou I, Farmaki E, Papavassiliou AG, Kiaris H. p53 antagonizes the unfolded protein response and inhibits ground glass hepatocyte development during endoplasmic reticulum stress. Exp Biol Med 2009; 237: 1173–80.
121. Duplan E, Giaime E, Viotti J, Sevalle J, Corti O, Brice A, et al. ERstress- 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 2013; 126: 2124–33.
122. Mlynarczyk C, Fahraeus R. Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of p21(CDKN1A). Nat Commun 2014; 5: 5067.
123. Thomas SE, Malzer E, Ordonez A, Dalton LE, van ’t Wout EF, Liniker E, et al. p53 and translation attenuation regulate distinct cell cycle checkpoints during endoplasmic reticulum (ER) stress. J Biol Chem 2013; 288: 7606–17.
124. Zhang F, Hamanaka RB, Bobrovnikova-Marjon E, Gordan JD, Dai MS, Lu H, et al. Ribosomal stress couples the unfolded protein response to p53-dependent cell cycle arrest. J Biol Chem 2006; 281: 30036–45.
125. Li J, Lee B, Lee AS. Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-upregulated modulator of apoptosis (PUMA) and NOXA by p53. J Biol Chem 2006; 281: 7260–70.
126. Bobrovnikova-Marjon E, Grigoriadou C, Pytel D, Zhang F, Ye J, Koumenis C, et al. PERK promotes cancer cell proliferation and tumor growth by limiting oxidative DNA damage. Oncogene 2010; 29: 3881–95.
127. Verfaillie T, Rubio N, Garg AD, Bultynck G, Rizzuto R, Decuypere JP, et al. PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death Differ 2012; 19: 1880–91.
128. Nagelkerke A, Bussink J, van der Kogel AJ, Sweep FC, Span PN. The PERK/ATF4/LAMP3-arm of the unfolded protein response affects radioresistance by interfering with the DNA damage response. Radiother Oncol 2013; 108: 415–21.
129. Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G. Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity 2013; 39: 74–88.
130. Marza E, Taouji S, Barroso K, Raymond AA, Guignard L, Bonneu M, et al. Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription. EMBO Rep 2015; 16: 332–40.
131. Periz G, Lu J, Zhang T, Kankel MW, Jablonski AM, Kalb R, et al. Regulation of protein quality control by UBE4B and LSD1 through p53-mediated transcription. PLoS Biol 2015; 13: e1002114.
132. Chhabra R, Dubey R, Saini N. Gene expression profiling indicate role of ER stress in miR-23a∼27a∼24-2 cluster induced apoptosis in HEK293T cells. RNA Biol 2011; 8: 648–64.
133. Yang F, Zhang L, Wang F, Wang Y, Huo XS, Yin YX, et al. Modulation of the unfolded protein response is the core of microRNA-122- involved sensitivity to chemotherapy in hepatocellular carcinoma. Neoplasia 2011; 13: 590–600.
134. Wang X, Guo B, Li Q, Peng J, Yang Z, Wang A, et al. miR-214 targets ATF4 to inhibit bone formation. Nat Med 2013; 19: 93–100.
135. Duan Q, Wang X, Gong W, Ni L, Chen C, He X, et al. ER stress negatively modulates the expression of the miR-199a/214 cluster to regulates tumor survival and progression in human hepatocellular cancer. PLoS One 2012; 7: e31518.
136. Ryu S, McDonnell K, Choi H, Gao D, Hahn M, Joshi N, et al. Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration. Cancer Cell 2013; 23: 63–76.
137. Gupta S, Read DE, Deepti A, Cawley K, Gupta A, Oommen D, et al. Perk-dependent repression of miR-106b-25 cluster is required for ER stress-induced apoptosis. Cell Death Dis 2012; 3: e333.
138. Byrd AE, Aragon IV, Brewer JW. MicroRNA-30c-2* limits expression of proadaptive factor XBP1 in the unfolded protein response. J Cell Biol 2012; 196: 689–98.
139. Chitnis NS, Pytel D, Bobrovnikova-Marjon E, Pant D, Zheng H, Maas NL, et al. miR-211 is a prosurvival microRNA that regulates chop expression in a PERK-dependent manner. Mol Cell 2012; 48: 353–64.
140. Sakaki K, Yoshina S, Shen X, Han J, DeSantis MR, Xiong M, et al. RNA surveillance is required for endoplasmic reticulum homeostasis. Proc Natl Acad Sci U S A 2012; 109: 8079–84.
141. Dejeans N, Pluquet O, Lhomond S, Grise F, Bouchecareilh M, Juin A, et al. Autocrine control of glioma cells adhesion and migration through IRE1alpha-mediated cleavage of SPARC mRNA. J Cell Sci 2012; 125: 4278–87.
142. Maurel M, Dejeans N, Taouji S, Chevet E, Grosset CF. MicroRNA- 1291-mediated silencing of IRE1alpha enhances Glypican-3 expression. RNA 2013; 19: 778–88.
143. Urra H, Dufey E, Lisbona F, Rojas-Rivera D, Hetz C. When ER stress reaches a dead end. Biochim Biophys Acta 2013; 1833: 3507–17.
144. Sandow JJ, Dorstyn L, O’Reilly LA, Tailler M, Kumar S, Strasser A, et al. ER stress does not cause upregulation and activation of caspase-2 to initiate apoptosis. Cell Death Differ 2013; 21: 475–80.
145. Li H, Yang BB. Stress response of glioblastoma cells mediated by miR-17-5p targeting PTEN and the passenger strand miR-17-3p targeting MDM2. Oncotarget 2013; 3: 1653–68.
146. Shan SW, Fang L, Shatseva T, Rutnam ZJ, Yang X, Du W, et al. Mature miR-17-5p and passenger miR-17-3p induce hepatocellular carcinoma by targeting PTEN, GalNT7 and vimentin in different signal pathways. J Cell Sci 2013; 126: 1517–30.
147. Yang X, Du WW, Li H, Liu F, Khorshidi A, Rutnam ZJ, et al. Both mature miR-17-5p and passenger strand miR-17-3p target TIMP3 and induce prostate tumor growth and invasion. Nucleic Acids Res 2013; 41: 9688–704.
148. Lichner Z, Saleh C, Subramaniam V, Seivwright A, Prud’homme GJ, Yousef GM. miR-17 inhibition enhances the formation of kidney cancer spheres with stem cell/tumor initiating cell properties. Oncotarget 2014; 6: 5567–81.
149. Park D, Lee SC, Park JW, Cho SY, Kim HK. Overexpression of miR- 17 in gastric cancer is correlated with proliferation-associated oncogene amplification. Pathol Int 2014; 64: 309–14.
150. Zhang J, Xiao Z, Lai D, Sun J, He C, Chu Z, et al. miR-21, miR-17 and miR-19a induced by phosphatase of regenerating liver-3 promote the proliferation and metastasis of colon cancer. Br J Cancer 2012; 107: 352–9.
151. Guo Y, Liu H, Zhang H, Shang C, Song Y. miR-96 regulates FOXO1-mediated cell apoptosis in bladder cancer. Oncol Lett 2013; 4: 561–5.
152. Fendler A, Jung M, Stephan C, Erbersdobler A, Jung K, Yousef GM. The antiapoptotic function of miR-96 in prostate cancer by inhibition of FOXO1. PLoS One 2013; 8: e80807.
153. Guttilla IK, White BA. Coordinate regulation of FOXO1 by miR- 27a, miR-96, and miR-182 in breast cancer cells. J Biol Chem 2009; 284: 23204–16.
154. Huang X, Lv W, Zhang JH, Lu DL. miR96 functions as a tumor suppressor gene by targeting NUAK1 in pancreatic cancer. Int J Mol Med 2014; 34: 1599–605