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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2011

Open Access 01-12-2011 | Review

Unfolded protein response in cancer: the Physician's perspective

Authors: Xuemei Li, Kezhong Zhang, Zihai Li

Published in: Journal of Hematology & Oncology | Issue 1/2011

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Abstract

The unfolded protein response ( UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic effects against cancer. In this review, we discuss the basic mechanisms of UPR and highlight the importance of UPR in cancer biology. We also update the UPR-targeted cancer therapeutics currently in clinical trials.
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Literature
1.
Kaufman RJ: Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev. 1999, 13: 1211-1233. 10.1101/gad.13.10.1211.PubMedCrossRef
2.
McMillan DR, Gething MJ, Sambrook J: The cellular response to unfolded proteins: intercompartmental signaling. Curr Opin Biotechnol. 1994, 5: 540-545. 10.1016/0958-1669(94)90071-X.PubMedCrossRef
3.
Mori K: Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell. 2000, 101: 451-454. 10.1016/S0092-8674(00)80855-7.PubMedCrossRef
4.
Ron D, Walter P: Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007, 8: 519-529. 10.1038/nrm2199.PubMedCrossRef
5.
Sidrauski C, Chapman R, Walter P: The unfolded protein response: an intracellular signalling pathway with many surprising features. Trends Cell Biol. 1998, 8: 245-249. 10.1016/S0962-8924(98)01267-7.PubMedCrossRef
6.
Rutkowski DT WJ, Back SH, Kaufman RJ: UPR Pathways Combine to Prevent Hepatic Steatosis Caused by ER Stress-Mediated Suppression of Transcriptional Master Regulators. Dev Cell. 2008, 15 (6): 829-40. 10.1016/j.devcel.2008.10.015.PubMedCentralPubMedCrossRef
7.
Wang G, Yang ZQ, Zhang K: Endoplasmic reticulum stress response in cancer: molecular mechanism and therapeutic potential. Am J Transl Res. 2010, 2: 65-74.PubMedCentralPubMed
8.
Scheuner DSB, Kaufman RJ: Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol Cell. 2001, 7 (6): 1165-76. 10.1016/S1097-2765(01)00265-9.PubMedCrossRef
9.
Dorner AJWL, Kaufman RJ: Increased synthesis of secreted proteins induces expression of glucose-regulated proteins in butyrate-treated Chinese hamster ovary cells. J Biol Chem. 1989, 264: 20602-20607.PubMed
10.
Schroder MKR: The mammalian unfolded protein response. Annu Rev Biochem. 2005, 74: 739-789. 10.1146/annurev.biochem.73.011303.074134.PubMedCrossRef
11.
Zhang KKR: Identification and characterization of endoplasmic reticulum stress-induced apoptosis in vivo. Methods Enzymol. 2008, 442: 395-419. full_text.PubMedCentralPubMedCrossRef
12.
13.
Travers KPC, Wodicka L, Lockhart DL, Weissman JS, Walter P: Functional and Genomic Analyses Reveal an Essential Coordination between the Unfolded Protein Response and ER-Associated Degradation. Cell. 2000, 101 (3): 249-258. 10.1016/S0092-8674(00)80835-1.PubMedCrossRef
14.
Brodsky SSVJL: One step at a time: endoplasmic reticulum-associated degradation. Nature Reviews Molecular Cell Biology. 2008, 9: 944-957. 10.1038/nrm2546.PubMedCentralPubMedCrossRef
15.
16.
Guzman M: Cannabinoids: potential anticancer agents. Nat Rev Cancer. 2003, 3: 745-755. 10.1038/nrc1188.PubMedCrossRef
17.
Velasco G, Carracedo A, Blazquez C, Lorente M, Aguado T, Haro A, Sanchez C, Galve-Roperh I, Guzman M: Cannabinoids and gliomas. Mol Neurobiol. 2007, 36: 60-67. 10.1007/s12035-007-0002-5.PubMedCrossRef
18.
Verfaillie T, Salazar M, Velasco G, Agostinis P: Linking ER Stress to Autophagy: Potential Implications for Cancer Therapy. Int J Cell Biol. 2010, 930509-
19.
Szegezdi E, Logue SE, Gorman AM, Samali A: Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep. 2006, 7: 880-885. 10.1038/sj.embor.7400779.PubMedCentralPubMedCrossRef
20.
Heather P, Harding YZ, Bertolotti Anne, Huiqing Zeng, David Ron: Perk Is Essential for Translational Regulation and Cell Survival during the Unfolded Protein Response. Molecular Cell. 2000, 5: 897-904. 10.1016/S1097-2765(00)80330-5.CrossRef
21.
Scheuner D, Song B, McEwen E, Liu C, Laybutt R, Gillespie P, Saunders T, Bonner-Weir S, Kaufman RJ: Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol Cell. 2001, 7: 1165-1176. 10.1016/S1097-2765(01)00265-9.PubMedCrossRef
22.
Wek RCCD: Translational control and the unfolded protein response. Antioxid Redox Signal. 2007, 9 (12): 2357-71. 10.1089/ars.2007.1764. 2007 9:2357-2371PubMedCrossRef
23.
24.
25.
Yan W, Frank CL, Korth MJ, Sopher BL, Novoa I, Ron D, Katze MG: Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK. Proc Natl Acad Sci USA. 2002, 99: 15920-15925. 10.1073/pnas.252341799.PubMedCentralPubMedCrossRef
26.
Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, Brown MS, Goldstein JL: ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell. 2000, 6: 1355-1364. 10.1016/S1097-2765(00)00133-7.PubMedCrossRef
27.
Lee AH, 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: 7448-7459. 10.1128/MCB.23.21.7448-7459.2003.PubMedCentralPubMedCrossRef
28.
Yamamoto KST, Matsui T, Sato M, Okada T, Yoshida H, Harada A, Mori K: Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1. Dev Cell. 2007, 13: 365-376. 10.1016/j.devcel.2007.07.018.PubMedCrossRef
29.
Lee K, Tirasophon W, Shen X, Michalak M, Prywes R, Okada T, Yoshida H, Mori K, Kaufman RJ: IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev. 2002, 16: 452-466. 10.1101/gad.964702.PubMedCentralPubMedCrossRef
30.
Rao RV, Bredesen DE: Misfolded proteins, endoplasmic reticulum stress and neurodegeneration. Curr Opin Cell Biol. 2004, 16: 653-662. 10.1016/j.ceb.2004.09.012.PubMedCentralPubMedCrossRef
31.
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: 881-891. 10.1016/S0092-8674(01)00611-0.PubMedCrossRef
32.
Rao RV, Castro-Obregon S, Frankowski H, Schuler M, Stoka V, del Rio G, Bredesen DE, Ellerby HM: Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway. J Biol Chem. 2002, 277: 21836-21842. 10.1074/jbc.M202726200.PubMedCrossRef
33.
Breckenridge DG, Germain M, Mathai JP, Nguyen M, Shore GC: Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene. 2003, 22: 8608-8618. 10.1038/sj.onc.1207108.PubMedCrossRef
34.
Ron D, Habener JF: CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev. 1992, 6: 439-453. 10.1101/gad.6.3.439.PubMedCrossRef
35.
Zinszner H, Kuroda M, Wang X, Batchvarova N, Lightfoot RT, Remotti H, Stevens JL, Ron D: CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev. 1998, 12: 982-995. 10.1101/gad.12.7.982.PubMedCentralPubMedCrossRef
36.
Marciniak SJ, Yun CY, Oyadomari S, Novoa I, Zhang Y, Jungreis R, Nagata K, Harding HP, Ron D: CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 2004, 18: 3066-3077. 10.1101/gad.1250704.PubMedCentralPubMedCrossRef
37.
Ma Y, Hendershot LM: The role of the unfolded protein response in tumour development: friend or foe?. Nat Rev Cancer. 2004, 4: 966-977. 10.1038/nrc1505.PubMedCrossRef
38.
Nakagawa TYJ: Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol. 2000, 150: 887-894. 10.1083/jcb.150.4.887.PubMedCentralPubMedCrossRef
39.
Morishima N, Nakanishi K, Takenouchi H, Shibata T, Yasuhiko Y: An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. J Biol Chem. 2002, 277: 34287-34294. 10.1074/jbc.M204973200.PubMedCrossRef
40.
Wu JKR: From acute ER stress to physiological roles of the Unfolded Protein Response. Cell Death Differ. 2006, 13 (3): 374-84. 10.1038/sj.cdd.4401840.PubMedCrossRef
41.
Davenport EL, Morgan GJ, Davies FE: Untangling the unfolded protein response. Cell Cycle. 2008, 7: 865-869. 10.4161/cc.7.7.5615.PubMedCrossRef
42.
Fernandez PM, Tabbara SO, Jacobs LK, Manning FC, Tsangaris TN, Schwartz AM, Kennedy KA, Patierno SR: Overexpression of the glucose-regulated stress gene GRP78 in malignant but not benign human breast lesions. Breast Cancer Res Treat. 2000, 59: 15-26. 10.1023/A:1006332011207.PubMedCrossRef
43.
Fels DR, Koumenis C: The PERK/eIF2alpha/ATF4 module of the UPR in hypoxia resistance and tumor growth. Cancer Biol Ther. 2006, 5: 723-728.PubMedCrossRef
44.
Haga N, Saito S, Tsukumo Y, Sakurai J, Furuno A, Tsuruo T, Tomida A: Mitochondria regulate the unfolded protein response leading to cancer cell survival under glucose deprivation conditions. Cancer Sci. 101: 1125-1132. 10.1111/j.1349-7006.2010.01525.x.
45.
Koumenis C, Wouters BG: "Translating" tumor hypoxia: unfolded protein response (UPR)-dependent and UPR-independent pathways. Mol Cancer Res. 2006, 4: 423-436. 10.1158/1541-7786.MCR-06-0150.PubMedCrossRef
46.
Romero-Ramirez L, Cao H, Nelson D, Hammond E, Lee AH, Yoshida H, Mori K, Glimcher LH, Denko NC, Giaccia AJ: XBP1 is essential for survival under hypoxic conditions and is required for tumor growth. Cancer Res. 2004, 64: 5943-5947. 10.1158/0008-5472.CAN-04-1606.PubMedCrossRef
47.
Shajahan AN, Riggins RB, Clarke R: The role of X-box binding protein-1 in tumorigenicity. Drug News Perspect. 2009, 22: 241-246. 10.1358/dnp.2009.22.5.1378631.PubMedCentralPubMedCrossRef
48.
Shuda M, Kondoh N, Imazeki N, Tanaka K, Okada T, Mori K, Hada A, Arai M, Wakatsuki T, Matsubara O: Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis. J Hepatol. 2003, 38: 605-614. 10.1016/S0168-8278(03)00029-1.PubMedCrossRef
49.
Song MS, Park YK, Lee JH, Park K: Induction of glucose-regulated protein 78 by chronic hypoxia in human gastric tumor cells through a protein kinase C-epsilon/ERK/AP-1 signaling cascade. Cancer Res. 2001, 61: 8322-8330.PubMed
50.
Sun S, Han J, Ralph WM, Chandrasekaran A, Liu K, Auborn KJ, Carter TH: Endoplasmic reticulum stress as a correlate of cytotoxicity in human tumor cells exposed to diindolylmethane in vitro. Cell Stress Chaperones. 2004, 9: 76-87.PubMedCentralPubMedCrossRef
51.
Chen Xiaoxin, Ding Yu, Chang-Gong Liu, and SM, Yang CS: Overexpression of glucose-regulated protein 94 (Grp94) in esophageal adenocarcinomas of a rat surgical model and humans. Carcinogenesis. 2002, 23: 123-130. 10.1093/carcin/23.1.123.PubMedCrossRef
52.
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: 411-416. 10.2174/156652409788167096.PubMedCrossRef
53.
54.
Qu L, Huang S, Baltzis D, Rivas-Estilla AM, Pluquet O, Hatzoglou M, Koumenis C, Taya Y, Yoshimura A, Koromilas AE: Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3beta. Genes Dev. 2004, 18: 261-277. 10.1101/gad.1165804.PubMedCentralPubMedCrossRef
55.
Kitamura M: Biphasic, bidirectional regulation of NF-kappaB by endoplasmic reticulum stress. Antioxid Redox Signal. 2009, 11: 2353-2364. 10.1089/ars.2008.2391.PubMedCrossRef
56.
Jolly C, Morimoto RI: Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst. 2000, 92: 1564-1572. 10.1093/jnci/92.19.1564.PubMedCrossRef
57.
58.
Dong D, Ni M, Li J, Xiong S, Ye W, Virrey JJ, Mao C, Ye R, Wang M, Pen L: Critical role of the stress chaperone GRP78/BiP in tumor proliferation, survival, and tumor angiogenesis in transgene-induced mammary tumor development. Cancer Res. 2008, 68: 498-505. 10.1158/0008-5472.CAN-07-2950.PubMedCrossRef
59.
Lee AS: GRP78 induction in cancer: therapeutic and prognostic implications. Cancer Res. 2007, 67: 3496-3499. 10.1158/0008-5472.CAN-07-0325.PubMedCrossRef
60.
Li J, Lee AS: Stress induction of GRP78/BiP and its role in cancer. Curr Mol Med. 2006, 6: 45-54. 10.2174/156652406775574523.PubMedCrossRef
61.
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. 22: 1099-1105. 10.1097/MEG.0b013e3283378405.
62.
Eunjung Lee PN, Spicer Darcy, Groshen Susan, Yu Mimi C, Lee Amy S: GRP78 as a Novel Predictor of Responsiveness Chemotherapy in Breast Cancer. Cancer Res. 2006, 66: 7849-10.1158/0008-5472.CAN-06-1660.PubMedCrossRef
63.
Fu Y, Lee AS: Glucose regulated proteins in cancer progression, drug resistance and immunotherapy. Cancer Biol Ther. 2006, 5: 741-744. 10.4161/cbt.5.7.2970.PubMedCrossRef
64.
Uramoto H, Sugio K, Oyama T, Nakata S, Ono K, Yoshimastu T, Morita M, Yasumoto K: Expression of endoplasmic reticulum molecular chaperone Grp78 in human lung cancer and its clinical significance. Lung Cancer. 2005, 49: 55-62. 10.1016/j.lungcan.2004.12.011.PubMedCrossRef
65.
Scriven P, Coulson S, Haines R, Balasubramanian S, Cross S, Wyld L: Activation and clinical significance of the unfolded protein response in breast cancer. Br J Cancer. 2009, 101: 1692-1698. 10.1038/sj.bjc.6605365.PubMedCentralPubMedCrossRef
66.
Wang Q, He Z, Zhang J, Wang Y, Wang T, Tong S, Wang L, Wang S, Chen Y: Overexpression of endoplasmic reticulum molecular chaperone GRP94 and GRP78 in human lung cancer tissues and its significance. Cancer Detect Prev. 2005, 29: 544-551. 10.1016/j.cdp.2005.09.010.PubMedCrossRef
67.
Langer R, Feith M, Siewert JR, Wester HJ, Hoefler H: Expression and clinical significance of glucose regulated proteins GRP78 (BiP) and GRP94 (GP96) in human adenocarcinomas of the esophagus. BMC Cancer. 2008, 8: 70-10.1186/1471-2407-8-70.PubMedCentralPubMedCrossRef
68.
Zheng HC, Takahashi H, Li XH, Hara T, Masuda S, Guan YF, Takano Y: Overexpression of GRP78 and GRP94 are markers for aggressive behavior and poor prognosis in gastric carcinomas. Hum Pathol. 2008, 39: 1042-1049. 10.1016/j.humpath.2007.11.009.PubMedCrossRef
69.
Jamora C, Dennert G, Lee AS: Inhibition of tumor progression by suppression of stress protein GRP78/BiP induction in fibrosarcoma B/C10ME. Proc Natl Acad Sci USA. 1996, 93: 7690-7694. 10.1073/pnas.93.15.7690.PubMedCentralPubMedCrossRef
70.
Davies MP, Barraclough DL, Stewart C, Joyce KA, Eccles RM, Barraclough R, Rudland PS, Sibson DR: Expression and splicing of the unfolded protein response gene XBP-1 are significantly associated with clinical outcome of endocrine-treated breast cancer. Int J Cancer. 2008, 123: 85-88. 10.1002/ijc.23479.PubMedCrossRef
71.
Gomez BP, Riggins RB, Shajahan AN, Klimach U, Wang A, Crawford AC, Zhu Y, Zwart A, Wang M, Clarke R: Human X-box binding protein-1 confers both estrogen independence and antiestrogen resistance in breast cancer cell lines. Faseb J. 2007, 21: 4013-4027. 10.1096/fj.06-7990com.PubMedCrossRef
72.
Carrasco DR, Sukhdeo K, Protopopova M, Sinha R, Enos M, Carrasco DE, Zheng M, Mani M, Henderson J, Pinkus GS: The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis. Cancer Cell. 2007, 11: 349-360. 10.1016/j.ccr.2007.02.015.PubMedCentralPubMedCrossRef
73.
Obeng EA, Carlson LM, Gutman DM, Harrington WJ, Lee KP, Boise LH: Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood. 2006, 107: 4907-4916. 10.1182/blood-2005-08-3531.PubMedCentralPubMedCrossRef
74.
Sterz JSO: The potential of proteasome inhibitors in cancer therapy. Expert Opin Investig Drugs. 2008, 17: 879-895. 10.1517/13543784.17.6.879.PubMedCrossRef
75.
Hoseki J, Ushioda R, Nagata K: Mechanism and components of endoplasmic reticulum-associated degradation. J Biochem. 2010, 147: 19-25. 10.1093/jb/mvp194.PubMedCrossRef
76.
77.
Lu DP, Christopher DA: Endoplasmic reticulum stress activates the expression of a sub-group of protein disulfide isomerase genes and AtbZIP60 modulates the response in Arabidopsis thaliana. Mol Genet Genomics. 2008, 280: 199-210. 10.1007/s00438-008-0356-z.PubMedCrossRef
78.
Townsend DM, Manevich Y, He L, Xiong Y, Bowers RR, Hutchens S, Tew KD: Nitrosative stress-induced s-glutathionylation of protein disulfide isomerase leads to activation of the unfolded protein response. Cancer Res. 2009, 69: 7626-7634. 10.1158/0008-5472.CAN-09-0493.PubMedCentralPubMedCrossRef
79.
Davenport EL, Moore HE, Dunlop AS, Sharp SY, Workman P, Morgan GJ, Davies FE: Heat shock protein inhibition is associated with activation of the unfolded protein response pathway in myeloma plasma cells. Blood. 2007, 110: 2641-2649. 10.1182/blood-2006-11-053728.PubMedCrossRef
80.
Banerji U, Judson I, Workman P: The clinical applications of heat shock protein inhibitors in cancer - present and future. Curr Cancer Drug Targets. 2003, 3: 385-390. 10.2174/1568009033481813.PubMedCrossRef
81.
Mimnaugh EG, Xu W, Vos M, Yuan X, Isaacs JS, Bisht KS, Gius D, Neckers L: Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity. Mol Cancer Ther. 2004, 3: 551-566.PubMedCrossRef
82.
Mimnaugh EG, Xu W, Vos M, Yuan X, Neckers L: Endoplasmic reticulum vacuolization and valosin-containing protein relocalization result from simultaneous hsp90 inhibition by geldanamycin and proteasome inhibition by velcade. Mol Cancer Res. 2006, 4: 667-681. 10.1158/1541-7786.MCR-06-0019.PubMedCrossRef
83.
Solit DB, Osman I, Polsky D, Panageas KS, Daud A, Goydos JS, Teitcher J, Wolchok JD, Germino FJ, Krown SE: Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with metastatic melanoma. Clin Cancer Res. 2008, 14: 8302-8307. 10.1158/1078-0432.CCR-08-1002.PubMedCentralPubMedCrossRef
84.
Usmani SZ, Bona RD, Chiosis G, Li Z: The anti-myeloma activity of a novel purine scaffold HSP90 inhibitor PU-H71 is via inhibition of both HSP90A and HSP90B1. J Hematol Oncol. 3: 40-10.1186/1756-8722-3-40.
85.
Pyrko P, Schonthal AH, Hofman FM, Chen TC, Lee AS: The unfolded protein response regulator GRP78/BiP as a novel target for increasing chemosensitivity in malignant gliomas. Cancer Res. 2007, 67: 9809-9816. 10.1158/0008-5472.CAN-07-0625.PubMedCrossRef
86.
Park HRTA, Sato S, Tsukumo Y, Yun J, Yamori T, Hayakawa Y, Tsuruo T, Shin-ya K: Effect on tumor cells of blocking survival response to glucose deprivation. J Natl Cancer Inst. 2004, 96 (17): 1300-10. 10.1093/jnci/djh243.PubMedCrossRef
87.
Matsuo J, Tsukumo Y, Sakurai J, Tsukahara S, Park HR, Shin-Ya K, Watanabe T, Tsuruo T, Tomida A: Preventing the unfolded protein response via aberrant activation of 4E-binding protein 1 by versipelostatin. Cancer Sci. 2008
88.
Saito S, Furuno A, Sakurai J, Sakamoto A, Park HR, Shin-Ya K, Tsuruo T, Tomida A: Chemical genomics identifies the unfolded protein response as a target for selective cancer cell killing during glucose deprivation. Cancer Res. 2009, 69: 4225-4234. 10.1158/0008-5472.CAN-08-2689.PubMedCrossRef
89.
Shin-Ya K: Novel antitumor and neuroprotective substances discovered by characteristic screenings based on specific molecular targets. Biosci Biotechnol Biochem. 2005, 69: 867-872. 10.1271/bbb.69.867.PubMedCrossRef
90.
Backer JM, Krivoshein AV, Hamby CV, Pizzonia J, Gilbert KS, Ray YS, Brand H, Paton AW, Paton JC, Backer MV: Chaperone-targeting cytotoxin and endoplasmic reticulum stress-inducing drug synergize to kill cancer cells. Neoplasia. 2009, 11: 1165-1173.PubMedCentralPubMedCrossRef
91.
Koong DFaAC: Irestatin, a potent inhibitor of IRE1 and the unfolded protein response, is a hypoxia-selective cytotoxin and impairs tumor growth. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2007, 25: 3514-
92.
Futamura Y, Tashiro E, Hironiwa N, Kohno J, Nishio M, Shindo K, Imoto M: Trierixin, a novel Inhibitor of ER stress-induced XBP1 activation from Streptomyces sp. II. structure elucidation. J Antibiot (Tokyo). 2007, 60: 582-585.CrossRef
93.
Patterson J, Palombella VJ, Fritz C, Normant E: IPI-504, a novel and soluble HSP-90 inhibitor, blocks the unfolded protein response in multiple myeloma cells. Cancer Chemother Pharmacol. 2008, 61: 923-932. 10.1007/s00280-007-0546-0.PubMedCrossRef
94.
Salazar M, Carracedo A, Salanueva IJ, Hernandez-Tiedra S, Lorente M, Egia A, Vazquez P, Blazquez C, Torres S, Garcia S: Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest. 2009, 119: 1359-1372. 10.1172/JCI37948.PubMedCentralPubMedCrossRef
95.
Liu BQ, Gao YY, Niu XF, Xie JS, Meng X, Guan Y, Wang HQ: Implication of unfolded protein response in resveratrol-induced inhibition of K562 cell proliferation. Biochem Biophys Res Commun. 2009, 391: 778-782. 10.1016/j.bbrc.2009.11.137.PubMedCrossRef
96.
Banjerdpongchai R, Kongtawelert P, Khantamat O, Srisomsap C, Chokchaichamnankit D, Subhasitanont P, Svasti J: Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells. J Hematol Oncol. 3: 50-10.1186/1756-8722-3-50.
97.
San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS: Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008, 359: 906-917. 10.1056/NEJMoa0801479.PubMedCrossRef
98.
Chauhan D, Singh AV, Ciccarelli B, Richardson PG, Palladino MA, Anderson KC: Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma. Blood. 115: 834-845. 10.1182/blood-2009-03-213009.
99.
O'Connor OA, Stewart AK, Vallone M, Molineaux CJ, Kunkel LA, Gerecitano JF, Orlowski RZ: A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clin Cancer Res. 2009, 15: 7085-7091.PubMedCentralPubMedCrossRef
100.
Lee AFW P, Burris HA, Papadopoulos K, Sausville EA, Rosen PJ, Mendelson DS, Infante JR, Patnaik A, Gordon MS: Updated results of a phase Ib/II study of carfilzomib (CFZ) in patients (pts) with relapsed malignancies. Journal of Clinical Oncology, 2010 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2010, 28: 8147-
101.
Paul G, Richardson BB, Berenson James: Phase II study of the proteasome inhibitor PS-341 in multiple myeloma (MM) patients (pts) with relapsed/refractory disease. Proc Am Soc Clin Oncol. 2002, 21 (abstr 40):
102.
Roberto Piva BR, Williams Michael: CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood. 2008, 111 (5): 2765-2775. 10.1182/blood-2007-07-100651.PubMedCrossRef
103.
Richardson PG, Badros AZ, Jagannath S, Tarantolo S, Wolf JL, Albitar M, Berman D, Messina M, Anderson KC: Tanespimycin with bortezomib: activity in relapsed/refractory patients with multiple myeloma. Br J Haematol. 150: 428-437.
104.
Richardson PG, Chanan-Khan AA, Alsina M, Albitar M, Berman D, Messina M, Mitsiades CS, Anderson KC: Tanespimycin monotherapy in relapsed multiple myeloma: results of a phase 1 dose-escalation study. Br J Haematol. 150: 438-445.
105.
Heath EI, Hillman DW, Vaishampayan U, Sheng S, Sarkar F, Harper F, Gaskins M, Pitot HC, Tan W, Ivy SP: A phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer. Clin Cancer Res. 2008, 14: 7940-7946. 10.1158/1078-0432.CCR-08-0221.PubMedCentralPubMedCrossRef
106.
Pacey S, Gore M, Chao D, Banerji U, Larkin J, Sarker S, Owen K, Asad Y, Raynaud F, Walton M: A Phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG, tanespimycin) in patients with metastatic melanoma. Invest New Drugs. 2010,
107.
Kummar S, Gutierrez ME, Gardner ER, Chen X, Figg WD, Zajac-Kaye M, Chen M, Steinberg SM, Muir CA, Yancey MA: Phase I trial of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein inhibitor, administered twice weekly in patients with advanced malignancies. Eur J Cancer. 46: 340-347. 10.1016/j.ejca.2009.10.026.
108.
Lancet JE, Gojo I, Burton M, Quinn M, Tighe SM, Kersey K, Zhong Z, Albitar MX, Bhalla K, Hannah AL, Baer MR: Phase I study of the heat shock protein 90 inhibitor alvespimycin (KOS-1022, 17-DMAG) administered intravenously twice weekly to patients with acute myeloid leukemia. Leukemia. 24: 699-705. 10.1038/leu.2009.292.
109.
Ramanathan RK, Egorin MJ, Erlichman C, Remick SC, Ramalingam SS, Naret C, Holleran JL, TenEyck CJ, Ivy SP, Belani CP: Phase I pharmacokinetic and pharmacodynamic study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin, an inhibitor of heat-shock protein 90, in patients with advanced solid tumors. J Clin Oncol. 28: 1520-1526. 10.1200/JCO.2009.25.0415.
110.
V. Zismanov LD, Gottfried M: Targeting ER-Golgi homeostasis as a therapeutic strategy in lung cancer. J Clin Oncol. 2010, suppl; abstr e21030
111.
Hanson BE, Vesole DH: Retaspimycin hydrochloride (IPI-504): a novel heat shock protein inhibitor as an anticancer agent. Expert Opin Investig Drugs. 2009, 18: 1375-1383. 10.1517/13543780903158934.PubMedCrossRef
112.
Caldas-Lopes E, Cerchietti L, Ahn JH, Clement CC, Robles AI, Rodina A, Moulick K, Taldone T, Gozman A, Guo Y: Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc Natl Acad Sci USA. 2009, 106: 8368-8373. 10.1073/pnas.0903392106.PubMedCentralPubMedCrossRef
113.
Marubayashi S, Koppikar P, Taldone T, Abdel-Wahab O, West N, Bhagwat N, Caldas-Lopes E, Ross KN, Gonen M, Gozman A: HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans. J Clin Invest. 120: 3578-3593. 10.1172/JCI42442.
114.
T. Bachleitner-Hofmann MYS, Chen C, Zeng Z: ntitumor activity of SNX-2112, a synthetic heat shock protein 90 inhibitor, in malignancies with amplification of the MET oncogene. J Clin Oncol. 2010, 28 (suppl; abstr e13561):
115.
Cross BC, McKibbin C, Callan AC, Roboti P, Piacenti M, Rabu C, Wilson CM, Whitehead R, Flitsch SL, Pool MR: Eeyarestatin I inhibits Sec61-mediated protein translocation at the endoplasmic reticulum. J Cell Sci. 2009, 122: 4393-4400. 10.1242/jcs.054494.PubMedCentralPubMedCrossRef
116.
Luo T, Wang J, Yin Y, Hua H, Jing J, Sun X, Li M, Zhang Y, Jiang Y: (-)-Epigallocatechin gallate sensitizes breast cancer cells to paclitaxel in a murine model of breast carcinoma. Breast Cancer Res. 12: R8-10.1186/bcr2473.
117.
D. Feldman ACK: Irestatin, a potent inhibitor of IRE1α and the unfolded protein response, is a hypoxia-selective cytotoxin and impairs tumor growth. Journal of Clinical Oncology. 2007, ASCO Annual Meeting Proceedings Part I, 25 (18S (June 20 Supplement)): 3514-2007
118.
Guzman M, Duarte MJ, Blazquez C, Ravina J, Rosa MC, Galve-Roperh I, Sanchez C, Velasco G, Gonzalez-Feria L: A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br J Cancer. 2006, 95: 197-203. 10.1038/sj.bjc.6603236.PubMedCentralPubMedCrossRef
Metadata
Title
Unfolded protein response in cancer: the Physician's perspective
Authors
Xuemei Li
Kezhong Zhang
Zihai Li
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2011
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-4-8

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