The Opposing Function of STAT3 as an Oncoprotein and Tumor Suppressor Is Dictated by the Expression Status of STAT3β in Esophageal Squamous Cell Carcinoma

Clinical Cancer Research

Volumn 22, Issue 3, 2016, Pages 691-703

  Zhang, Hai Feng ^a,b   Chen, Ye ^a   Wu, Chengsheng ^b   Wu, Zhi Yong ^c   Tweardy, David J ^d   Alshareef, Abdulraheem ^b   Liao, Lian Di ^a   Xue, Yu Jie ^a   Wu, Jian Yi ^a   Chen, Bo ^a   Xu, Xiu E ^a   Gopal, Keshav ^b   Gupta, Nidhi ^b   Li, En Min ^a   Xu, Li Yan ^a   Lai, Raymond ^b,e  

^a SHANTOU UNIVERSITY MEDICAL COLLEGE   (China)

^b UNIVERSITY OF ALBERTA   (Canada)

^c SHANTOU CENTRAL HOSPITAL   (China)

^d UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^e DynaLIFE Dx   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CISPLATIN; FLUOROURACIL; HETERODIMER; HOE 33342; ONCOPROTEIN; PROTEIN TYROSINE PHOSPHATASE; PTP MEG2 PROTEIN; STAT3 ALPHA PROTEIN; STAT3 BETA PROTEIN; STAT3 PROTEIN; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER PROGNOSIS; CANCER STEM CELL; CHEMOSENSITIVITY; CHROMATIN IMMUNOPRECIPITATION; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DISEASE MARKER; DNA BINDING; ESOPHAGEAL SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; IN VITRO STUDY; IN VIVO STUDY; MAJOR CLINICAL STUDY; MALE; MOUSE; NONHUMAN; OVERALL SURVIVAL; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; RECURRENCE FREE SURVIVAL; STAINING; TRANSCRIPTION TERMINATION; TUMOR XENOGRAFT; ANIMAL; BIOLOGICAL MODEL; CARCINOMA, SQUAMOUS CELL; CHEMISTRY; DISEASE MODEL; DRUG RESISTANCE; DRUG SCREENING; ESOPHAGEAL NEOPLASMS; GENE EXPRESSION REGULATION; GENETICS; IMMUNOHISTOCHEMISTRY; METABOLISM; MORTALITY; PHOSPHORYLATION; PROGNOSIS; PROTEIN MULTIMERIZATION; TRANSCRIPTION INITIATION; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOMA, SQUAMOUS CELL; CELL LINE, TUMOR; DISEASE MODELS, ANIMAL; DRUG RESISTANCE, NEOPLASM; ESOPHAGEAL NEOPLASMS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IMMUNOHISTOCHEMISTRY; MODELS, BIOLOGICAL; NEOPLASTIC STEM CELLS; ONCOGENE PROTEINS; PHOSPHORYLATION; PROGNOSIS; PROTEIN MULTIMERIZATION; PROTEIN TYROSINE PHOSPHATASES; STAT3 TRANSCRIPTION FACTOR; TRANSCRIPTIONAL ACTIVATION; TUMOR SUPPRESSOR PROTEINS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84959017357     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-15-1253     Document Type: Article

References (45)

1. Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: Role of STAT3 in the tumour microenvironment. Nat Rev Immunol 2007;7:41-51.
2. Yu H, Jove R. The STATs of cancer-new molecular targets come of age. Nat Rev Cancer 2004;4:97-105.
3. Zhang HF, Lai R. STAT3 in cancer-friend or foe? Cancers (Basel) 2014;6:1408-40.
4. Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, et al. Stat3 as an oncogene. Cell 1999;98:295-303.
5. MusteanuM, Blaas L, Mair M, Schlederer M, BilbanM, Tauber S, et al. Stat3 is a negative regulator of intestinal tumor progression in Apc(Min) mice. Gastroenterology 2010;138:1003-11.
6. Lee J, Kim JC, Lee SE, Quinley C, KimH,Herdman S, et al. Signal transducer and activator of transcription 3 (STAT3) protein suppresses adenoma-tocarcinoma transition in ApcMin/+ mice via regulation of Snail-1 (SNAI) protein stability. J Biol Chem 2012;287:18182-9.
7. Couto JP, Daly L, Almeida A, Knauf JA, Fagin JA, Sobrinho-SimoesM, et al. STAT3 negatively regulates thyroid tumorigenesis. Proc Natl Acad Sci U S A 2012;109:E2361-70.
8. Clifford JL, Menter DG, Yang X, Walch E, Zou C, Clayman GL, et al. Expression of protein mediators of type I interferon signaling in human squamous cell carcinoma of the skin. Cancer Epidemiol Biomarkers Prev 2000;9:993-7.
9. Pectasides E, Egloff AM, Sasaki C, Kountourakis P, Burtness B, Fountzilas G, et al. Nuclear localization of signal transducer and activator of transcription 3 in head and neck squamous cell carcinoma is associated with a better prognosis. Clin Cancer Res 2010;16:2427-34.
10. Ettl T, Stiegler C, Zeitler K, Agaimy A, Zenk J, Reichert TE, et al. EGFR, HER2, survivin, and loss of p-STAT3 characterize high-grade malignancy in salivary gland cancer with impact on prognosis. Hum Pathol 2012;43: 921-31.
11. Dolled-Filhart M, Camp RL, Kowalski DP, Smith BL, Rimm DL. Tissue microarray analysis of signal transducers and activators of transcription 3 (Stat3) and phospho-Stat3(Tyr705) in node-negative breast cancer shows nuclear localization is associated with a better prognosis. Clin Cancer Res 2003;9:594-600.
12. Sato T, Neilson LM, Peck AR, Liu C, Tran TH, Witkiewicz A, et al. Signal transducer and activator of transcription-3 and breast cancer prognosis.Am J Cancer Res 2011;1:347-55.
13. Hsiao JR, Jin YT, Tsai ST, Shiau AL, Wu CL, Su WC. Constitutive activation of STAT3 and STAT5 is present in the majority of nasopharyngeal carcinoma and correlates with better prognosis. Br J Cancer 2003;89:344-9.
14. Gordziel C, Bratsch J, Moriggl R, Knosel T, Friedrich K. Both STAT1 and STAT3 are favourable prognostic determinants in colorectal carcinoma. Br J Cancer 2013;109:138-46.
15. Schaefer TS, Sanders LK,Nathans D. Cooperative transcriptional activity of Jun and Stat3 beta, a short form of Stat3. Proc Natl Acad Sci U S A 1995; 92:9097-101.
16. Caldenhoven E, Van Dijk TB, Solari R, Armstrong J, Raaijmakers JA, Lammers JW, et al. STAT3beta, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription. J Biol Chem1996; 271:13221-7.
17. Schaefer TS, Sanders LK, Park OK, Nathans D. Functional differences between Stat3alpha and Stat3beta. Mol Cell Biol 1997;17:5307-16.
18. Shao H, Quintero AJ, Tweardy DJ. Identification and characterization of cis elements in the STAT3 gene regulating STAT3 alpha and STAT3 beta messenger RNA splicing. Blood 2001;98:3853-6.
19. Niu G, Heller R, Catlett-Falcone R, Coppola D, Jaroszeski M, Dalton W, et al. Gene therapy with dominant-negative Stat3 suppresses growth of the murine melanoma B16 tumor in vivo. Cancer Res 1999; 59:5059-63.
20. Niu G, Shain KH, Huang M, Ravi R, Bedi A, Dalton WS, et al. Overexpression of a dominant-negative signal transducer and activator of transcription 3 variant in tumor cells leads to production of soluble factors that induce apoptosis and cell cycle arrest. Cancer Res 2001;61:3276-80.
21. Ivanov VN, Bhoumik A, Krasilnikov M, Raz R, Owen-Schaub LB, Levy D, et al. Cooperation between STAT3 and c-jun suppresses Fas transcription. Mol Cell 2001;7:517-28.
22. Ivanov VN, Zhou H, Partridge MA, Hei TK. Inhibition of ataxia telangiectasia mutated kinase activity enhances trail-mediated apoptosis in human melanoma cells. Cancer Res 2009;69:3510-9.
23. Zammarchi F, De Stanchina E, Bournazou E, Supakorndej T, Martires K, Riedel E, et al. Antitumorigenic potential of STAT3 alternative splicing modulation. Proc Natl Acad Sci U S A 2011;108:17779-84.
24. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
25. Zhang Y, Du XL, Wang CJ, Lin DC, Ruan X, Feng YB, et al. Reciprocal activation between PLK1 and Stat3 contributes to survival and proliferation of esophageal cancer cells. Gastroenterology 2012;142: 521-30.e3.
26. Chen X, Ying Z, Lin X, LinH,Wu J, LiM, et al. Acylglycerol kinase augments JAK2/STAT3 signaling in esophageal squamous cells. J Clin Invest 2013; 123:2576-89.
27. Wang Z, Zhu S, Shen M, Liu J, Wang M, Li C, et al. STAT3 is involved in esophageal carcinogenesis through regulation of Oct-1. Carcinogenesis 2013;34:678-88.
28. Timme S, Ihde S, Fichter CD, Waehle V, Bogatyreva L, Atanasov K, et al. STAT3 expression, activity and functional consequences of STAT3 inhibition in esophageal squamous cell carcinomas and Barrett's adenocarcinomas. Oncogene 2014;33:3256-66.
29. Bharadwaj U, KasembeliMM, Eckols TK, Kolosov M, Lang P, Christensen K, et al. Monoclonal antibodies specific for STAT3b reveal its contribution to constitutive STAT3 phosphorylation in breast cancer. Cancers (Basel) 2014;6:2012-34.
30. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: Accumulating evidence and unresolved questions. Nat Rev Cancer 2008;8:755-68.
31. Zhao JS, Li WJ, Ge D, Zhang PJ, Li JJ, Lu CL, et al. Tumor initiating cells in esophageal squamous cell carcinomas express high levels of CD44. PLoS One 2011;6:e21419.
32. Su F, Ren F, Rong Y, Wang Y, Geng Y, Wang Y, et al. Protein tyrosine phosphatase Meg2 dephosphorylates signal transducer and activator of transcription 3 and suppresses tumor growth in breast cancer. Breast Cancer Res 2012;14:R38.
33. Hashimoto Y, Ito T, Inoue H, Okumura T, Tanaka E, Tsunoda S, et al. Prognostic significance of fascin overexpression in human esophageal squamous cell carcinoma. Clin Cancer Res 2005;11:2597-605.
34. Park OK, Schaefer LK, Wang W, Schaefer TS. Dimer stability as a determinant of differential DNA binding activity of Stat3 isoforms. J Biol Chem 2000;275:32244-9.
35. Ng IH, Ng DC, Jans DA, Bogoyevitch MA. Selective STAT3-a or-b expression reveals spliceform-specific phosphorylation kinetics, nuclear retention and distinct gene expression outcomes. Biochem J 2012;447: 125-36.
36. Maritano D, Sugrue ML, Tininini S, Dewilde S, Strobl B, Fu X, et al. The STAT3 isoforms a and b have unique and specific function. Nat Immunol 2004;5:401-9.
37. Schneller D,Machat G, Sousek A, Proell V, Van Zijl F, Zulehner G, et al. P19 (ARF)/p14(ARF) controls oncogenic functions of signal transducer and activator of transcription 3 in hepatocellular carcinoma. Hepatology 2011;54:164-72.
38. Ecker A, Simma O, Hoelbl A, Kenner L, Beug H, Moriggl R, et al. The dark and the bright side of Stat3: Proto-oncogene and tumor-suppressor. Front Biosci 2009;14:2944-58.
39. Niu G, Wright KL,Ma Y, WrightGM, Huang M, Irby R, et al. Role of Stat3 in regulating p53 expression and function. Mol Cell Biol 2005;25:7432-40.
40. Burke WM, Jin X, Lin HJ, Huang M, Liu R, Reynolds RK, et al. Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells. Oncogene 2001;20:7925-34.
41. Turkson J, Bowman T, Garcia R, Caldenhoven E, De Groot RP, Jove R. Stat3 activation by Src induces specific gene regulation and is required for cell transformation. Mol Cell Biol 1998;18:2545-52.
42. Zhang YW, Wang LM, Jove R, Vande Woude GF. Requirement of Stat3 signaling for HGF/SF-Met mediated tumorigenesis. Oncogene 2002;21: 217-26.
43. Bowman T, Broome MA, Sinibaldi D, Wharton W, Pledger WJ, Sedivy JM, et al. Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc Natl Acad Sci U S A 2001; 98:7319-24.
44. Marino F, Orecchia V, Regis G, Musteanu M, Tassone B, Jon C, et al. STAT3b controls inflammatory responses and early tumor onset in skin and colon experimental cancer models. Am J Cancer Res 2014;4:484-94.
45. Kaptein A, Paillard V, Saunders M. Dominant negative stat3 mutant inhibits interleukin-6-induced Jak-STAT signal transduction. J Biol Chem 1996;271:5961-4.