XPO1 (CRM1) inhibition represses STAT3 activation to drive a survivin-dependent oncogenic switch in triple-negative breast cancer

Molecular Cancer Therapeutics

Volumn 13, Issue 3, 2014, Pages 675-686

  Cheng, Yan ^a   Holloway, Michael P ^a   Nguyen, Kevin ^a   McCauley, Dilara ^b   Landesman, Yosef ^b   Kauffman, Michael G ^b   Shacham, Sharon ^b   Altura, Rachel A ^a  

^a BROWN UNIVERSITY   (United States)

^b Karyopharm Therapeutics   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CASPASE 3; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN BINDING PROTEIN; EXPORTIN 1; FLUOROURACIL; KPT 185; KPT 251; KPT 276; KPT 330; PROTEIN INHIBITOR; STAT3 PROTEIN; SURVIVIN; UNCLASSIFIED DRUG;

ACETYLATION; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CANCER CHEMOTHERAPY; CANCER GROWTH; CELL NUCLEUS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOSE TIME EFFECT RELATION; DRUG BLOOD LEVEL; EMBRYO; ESTROGEN RECEPTOR POSITIVE BREAST CANCER; FEMALE; GENE REPRESSION; GENE SWITCHING; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; MOLECULARLY TARGETED THERAPY; MOUSE; NONHUMAN; NUCLEAR EXPORT SIGNAL; PHASE 1 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROMOTER REGION; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; TRANSACTIVATION; TRANSCRIPTION INITIATION; TRIPLE NEGATIVE BREAST CANCER;

ACTIVE TRANSPORT, CELL NUCLEUS; APOPTOSIS; CASPASE 3; CELL LINE, TUMOR; CELL NUCLEUS; FEMALE; GENETIC THERAPY; HUMANS; INHIBITOR OF APOPTOSIS PROTEINS; KARYOPHERINS; RECEPTORS, CYTOPLASMIC AND NUCLEAR; STAT3 TRANSCRIPTION FACTOR; TRIPLE NEGATIVE BREAST NEOPLASMS;

EID: 84896284216     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-13-0416     Document Type: Article

References (52)

1. Fukuda M, Asano S, Nakamura T, Adachi M, Yoshida M, Yanagida M, et al. CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature 1997;390:308-11. (Pubitemid 27513316)
2. Fornerod M, Ohno M, Yoshida M, Mattaj IW. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 1997;90:1051-60. (Pubitemid 27408519)
3. Xu D, Grishin N, Chook Y. NESdb: a database of NES-containing CRM1 cargoes. Mol Biol Cell 2012;23:3673-6.
4. Fu SC, Huang HC, Horton P, Juan HF. ValidNESs: a database of validated leucine-rich nuclear export signals. Nucleic Acids Res 2013; 41:D338-43.
5. Freedman DA, Levine AJ. Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6. Mol Cell Biol 1998;18:7288-93. (Pubitemid 28533048)
6. Sato N, Tsuruma R, Imoto S, Sekine Y, Muromoto R, Sugiyama K, et al. Nuclear retention of STAT3 through the coiled-coil domain regulates its activity. Biochem Biophys Res Commun 2005;336: 617-24. (Pubitemid 41267271)
7. Rodriguez JA, Span SW, Ferreira CG, Kruyt FA, Giaccone G. CRM1- mediated nuclear export determines the cytoplasmic localization of the antiapoptotic protein Survivin. Exp Cell Res 2002;275:44-53.
8. Latre de Late P, Pepin A, Assaf-Vandecasteele H, Espinasse C, Nicolas V, Asselin-Labat ML, et al. Glucocorticoid-induced leucine zipper (GILZ) promotes the nuclear exclusion of FOXO3 in a Crm1-dependent manner. J Biol Chem 2010;285:5594-605.
9. Dohi T, Okada K, Xia F, Wilford CE, Samuel T, Welsh K, et al. An IAP-IAP complex inhibits apoptosis. J Biol Chem 2004;279:34087-90. (Pubitemid 39318028)
10. Tanaka K, Iwamoto S, Gon G, Nohara T, Iwamoto M, Tanigawa N. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res 2000;6:127-34. (Pubitemid 30064984)
11. Stauber RH, Rabenhorst U, Rekik A, Engels K, Bier C, Knauer SK. Nucleocytoplasmic shuttling and the biological activity of mouse survivin are regulated by an active nuclear export signal. Traffic 2006; 7:1461-72. (Pubitemid 44524519)
12. Chan KS, Wong CH, Huang YF, Li HY. Survivin withdrawal by nuclear export failure as a physiological switch to commit cells to apoptosis. Cell Death Dis 2010;1:e57.
13. Wang H, Holloway M, Ma L, Cooper Z, Riolo M, Samkari A, et al. Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity. J Biol Chem 2010;285:36129-37.
14. Knauer SK, Kramer OH, Knosel T, Engels K, Rodel F, Kovacs AF, et al. Nuclear export is essential for the tumor-promoting activity of survivin. FASEB J 2007;21:207-16. (Pubitemid 46052558)
15. Bromberg J, Darnell JE Jr. The role of STATs in transcriptional control and their impact on cellular function. Oncogene 2000;19:2468-73. (Pubitemid 30339202)
16. Diaz N, Minton S, Cox C, Bowman T, Gritsko T, Garcia R, et al. Activation of stat3 in primary tumors from high-risk breast cancer patients is associated with elevated levels of activated SRC and survivin expression. Clin Cancer Res 2006;12:20-8. (Pubitemid 43166171)
17. Gritsko T, Williams A, Turkson J, Kaneko S, Bowman T, Huang M, et al. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells. Clin Cancer Res 2006;12:11-9. (Pubitemid 43166170)
18. Zhang X, Yue P, Page B, Li T, Zhao W, Namanja A, et al. Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts. Proc Natl Acad Sci USA 2012;109:9623 -8.
19. Song H, Wang R, Wang S, Lin J. A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells. Proc Natl Acad Sci U S A 2005;102:4700-5. (Pubitemid 40471517)
20. Siddiquee K, Zhang S, Guida W, Blaskovich M, Greedy B, Lawrence H, et al. Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity. Proc Natl Acad Sci U S A 2007;104:7391-6. (Pubitemid 47185916)
21. Bhattacharya S, Schindler C. Regulation of Stat3 nuclear export. J Clin Invest 2003;111:553-9. (Pubitemid 36228012)
22. Kudo N, Matsumori N, Taoka H, Fujiwara D, Schreiner E, Wolff B, et al. Leptomycin B in activates CRM1/export in 1 by covalent modification at a cysteine residue in the central conserved region. Proc Natl Acad Sci U S A 1999;96:9112-7. (Pubitemid 29374716)
23. Mutka SC, Yang WQ, Dong SD, Ward SL, Craig DA, Timmermans PB, et al. Identification of nuclear export inhibitors with potent anticancer activity in vivo. Cancer Res 2009;69:510-7.
24. Sun Q, Carrasco Y, Hu Y, Guo X, Mirzaei H, Macmillan J, et al. Nuclear export inhibition through covalent conjugation and hydrolysis of Leptomycin B by CRM1. Proc Natl Acad Sci U S A 2013;110:1303 -8.
25. Lapalombella R, Sun Q, Williams K, Tangeman L, Jha S, Zhong Y, et al. Selective inhibitors of nuclear export show that CRM1/XPO1 is a target in chronic lymphocytic leukemia. Blood 2012;120:4621-34.
26. Zhang K, Wang M, Tamayo AT, Shacham S, Kauffman M, Lee J, et al. Novel selective inhibitors of nuclear export CRM1 antagonists for therapy in mantle cell lymphoma. Exper Hematology 2013;41: 67-78 e4.
27. Riolo M,Cooper Z, Holloway M, Cheng Y, Bianchi C, Yakirevich E, et al. Histone deacetylase 6 (HDAC6) deacetylates survivin for its nuclear export in breast cancer. J Biol Chem 2012;287:10885-93.
28. Schagger H. Tricine-SDS-PAGE. Nat Protocols 2006;1:16-22.
29. Azmi A, Aboukameel A, Bao B, Sarkar F, Philip P, Kauffman M, et al. Selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice. Gastroenterology 2013;144:447-56.
30. Zhao J, Tenev T, Martins LM, Downward J, Lemoine NR. The ubiquitin-proteasome pathway regulates survivin degradation in a cell cycledependent manner. J Cell Sci 2000;113:4363-71. (Pubitemid 32000697)
31. Yang Y, Fang S, Jensen JP, Weissman AM, Ashwell JD. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 2000;288:874-7. (Pubitemid 30257739)
32. Arora V, Cheung HH, Plenchette S, Micali OC, Liston P, Korneluk RG. Degradation of survivin by the X-linked inhibitor of apoptosis (XIAP)- XAF1 complex. J Biol Chem 2007;282:26202- 9.
33. Yuan ZL, Guan YJ, Chatterjee D, Chin YE. Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science 2005;307: 269-73. (Pubitemid 40116244)
34. Turner J, Dawson J, Sullivan D. Nuclear export of proteins and drug resistance in cancer. Biochem Pharm 2012;83:1021-32.
35. Fabbro M, Henderson B. Regulation of tumor suppressors by nuclear-cytoplasmic shuttling. Exper Cell Res 2003;282:59-69. (Pubitemid 36259901)
36. Noske A, Weichert W, Niesporek S, R €oske A, Buckendahl A-C, Koch I, et al. Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo 1 is a prognostic factor in human ovarian cancer. Cancer 2008;112:1733-43. (Pubitemid 351536833)
37. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-49.
38. Xu C, Yamamoto-Ibusuki M, Yamamoto Y, Yamamoto S, Fujiwara S, Murakami K, et al. High survivin mRNA expression is a predictor of poor prognosis in breast cancer: a comparative study at the mRNA and protein level. Breast Cancer. Epub 2012 Sep 12.
39. Kennedy SM, O'Driscoll L, Purcell R, Fitz-Simons N, McDermott EW, Hill AD, et al. Prognostic importance of survivin in breast cancer. Br J Cancer 2003;88:1077-83. (Pubitemid 36560779)
40. Span PN, Sweep FC, Wiegerinck ET, Tjan-Heijnen VC, Manders P, Beex LV, et al. Survivin is an independent prognostic marker for risk stratification of breast cancer patients. Clin Chem 2004;50: 1986-93. (Pubitemid 39425834)
41. Lu C, Shao C, Cobos E, Singh KP, Gao W. Chemotherapeutic sensitization of leptomycin B resistant lung cancer cells by pretreatment with doxorubicin. PLoS ONE 2012;7:e32895.
42. Bromberg J. Stat proteins and oncogenesis. J Clin Invest 2002;109: 1139-42. (Pubitemid 34496590)
43. Turkson J, Jove R. STAT proteins: novel molecular targets for cancer drug discovery. Oncogene 2000;19:6613-26. (Pubitemid 32197700)
44. Zhang X, Yue P, Fletcher S, Zhao W, Gunning PT, Turkson J. A novel small-molecule disrupts Stat3 SH2 domain-phosphotyrosine interactions and Stat3-dependent tumor processes. Biochem Pharmacol 2010;79:1398- 409.
45. Nicholson D, Ali A, Thornberry N, Vaillancourt J, Ding C, Gallant M, et al. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 1995;376:37-43.
46. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase- 9 complex initiates an apoptotic protease cascade. Cell 1997; 91:479-89. (Pubitemid 27508237)
47. Janicke RU, Walker PA, Lin XY, Porter AG. Specific cleavage of the retinoblastoma protein by an ICE-like protease in apoptosis. EMBO J 1996;15:6969- 78.
48. Chen L, Marechal V, Moreau J, Levine AJ, Chen J. Proteolytic cleavage of the mdm2 oncoprotein during apoptosis. J Biol Chem 1997; 272:22966-73. (Pubitemid 27386122)
49. Levkau B, Koyama H, Raines EW, Clurman BE, Herren B, Orth K, et al. Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: role of a caspase cascade. Mol Cell 1998;1:553 -63.
50. Darnowski JW, Goulette FA, Guan YJ, Chatterjee D, Yang ZF, Cousens LP, et al. Stat3 cleavage by caspases: impact on full-length Stat3 expression, fragment formation, and transcriptional activity. J Biol Chem 2006;281:17707-17. (Pubitemid 44035569)
51. Verspurten J, Gevaert K, Declercq W, Vandenabeele P. Site predicting the cleavage of proteinase substrates. Trends Biochem Sci 2009;34: 319-23.
52. Wee LJ, Tan TW, Ranganathan S. SVM-based prediction of caspase substrate cleavage sites. BMC Bioinformatics 2006;7:S14.