EIF5A2 Predicts Outcome in Localised Invasive Bladder Cancer and Promotes Bladder Cancer Cell Aggressiveness in Vitro and in Vivo

Overview

Journal Br J Cancer

Specialty Oncology

Date 2014 Feb 8

PMID 24504366

Citations 38

Authors

J-H Wei

J-Z Cao

D Zhang

B Liao

W-M Zhong

J Lu

H-W Zhao

J-X Zhang

Z-T Tong

S Fan

C-Z Liang

Y-B Liao

J Pang

R-H Wu

Y Fang

Z-H Chen

B Li

D Xie

W Chen

J-H Luo

Affiliations

Soon will be listed here.

Abstract

Background: EIF5A2, eukaryotic translation initiation factor 5A2, is associated with several human cancers. In this study, we investigated the role of EIF5A2 in the metastatic potential of localised invasive bladder cancer (BC) and its underlying molecular mechanisms were explored.

Methods: The expression pattern of EIF5A2 in localised invasive BC was determined by immunohistochemistry. In addition, the function of EIF5A2 in BC and its underlying mechanisms were elucidated with a series of in vitro and in vivo assays.

Results: Overexpression of EIF5A2 was an independent predictor for poor metastasis-free survival of localised invasive BC patients treated with radical cystectomy. Knockdown of EIF5A2 inhibited BC cell migratory and invasive capacities in vitro and metastatic potential in vivo and reversed epithelial-mesenchymal transition (EMT), whereas overexpression of EIF5A2 promoted BC cells motility and invasiveness in vitro and metastatic potential in vivo and induced EMT. In addition, we found that EIF5A2 might activate TGF-β1 expression to induce EMT and drive aggressiveness in BC cells. EIF5A2 stabilized STAT3 and stimulated nuclear localisation of STAT3, which resulted in increasing enrichment of STAT3 onto TGF-β1 promoter to enhance the transcription of TGF-β1.

Conclusions: EIF5A2 overexpression predicts tumour metastatic potential in patients with localised invasive BC treated with radical cystectomy. Furthermore, EIF5A2 elevated TGF-β1 expression through STAT3 to induce EMT and promotes aggressiveness in BC.

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References

Tong Z, Cai M, Wang X, Kong L, Mai S, Liu Y . EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin. Oncogene. 2011; 31(5):583-94. DOI: 10.1038/onc.2011.254. View

Guan X, Fung J, Ma N, Lau S, Tai L, Xie D . Oncogenic role of eIF-5A2 in the development of ovarian cancer. Cancer Res. 2004; 64(12):4197-200. DOI: 10.1158/0008-5472.CAN-03-3747. View

He L, Zhao H, Li B, Liu Y, Liu M, Guan X . Overexpression of eIF5A-2 is an adverse prognostic marker of survival in stage I non-small cell lung cancer patients. Int J Cancer. 2010; 129(1):143-50. DOI: 10.1002/ijc.25669. View

Kim Y, Ratziu V, Choi S, Lalazar A, THEISS G, Dang Q . Transcriptional activation of transforming growth factor beta1 and its receptors by the Kruppel-like factor Zf9/core promoter-binding protein and Sp1. Potential mechanisms for autocrine fibrogenesis in response to injury. J Biol Chem. 1998; 273(50):33750-8. DOI: 10.1074/jbc.273.50.33750. View

Lin W, Tsai W, Shao R, Wu G, Peng L, Barlow L . Hepatitis C virus regulates transforming growth factor beta1 production through the generation of reactive oxygen species in a nuclear factor kappaB-dependent manner. Gastroenterology. 2010; 138(7):2509-18, 2518.e1. PMC: 2883661. DOI: 10.1053/j.gastro.2010.03.008. View

Wendt M, Schiemann B, Parvani J, Lee Y, Kang Y, Schiemann W . TGF-β stimulates Pyk2 expression as part of an epithelial-mesenchymal transition program required for metastatic outgrowth of breast cancer. Oncogene. 2012; 32(16):2005-15. PMC: 3721373. DOI: 10.1038/onc.2012.230. View

Chen W, Luo J, Hua W, Zhou F, Lin M, Kung H . Overexpression of EIF-5A2 is an independent predictor of outcome in patients of urothelial carcinoma of the bladder treated with radical cystectomy. Cancer Epidemiol Biomarkers Prev. 2009; 18(2):400-8. DOI: 10.1158/1055-9965.EPI-08-0754. View

Guan X, Sham J, Tang T, Fang Y, Huo K, Yang J . Isolation of a novel candidate oncogene within a frequently amplified region at 3q26 in ovarian cancer. Cancer Res. 2001; 61(9):3806-9. View

Ogata H, Chinen T, Yoshida T, Kinjyo I, Takaesu G, Shiraishi H . Loss of SOCS3 in the liver promotes fibrosis by enhancing STAT3-mediated TGF-beta1 production. Oncogene. 2006; 25(17):2520-30. DOI: 10.1038/sj.onc.1209281. View

10.

Eder I, Stenzl A, Hobisch A, Cronauer M, Bartsch G, Klocker H . Transforming growth factors-beta 1 and beta 2 in serum and urine from patients with bladder carcinoma. J Urol. 1996; 156(3):953-7. View

11.

Nguyen D, Bos P, Massague J . Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009; 9(4):274-84. DOI: 10.1038/nrc2622. View

12.

Shariat S, Kim J, Andrews B, Kattan M, Wheeler T, Kim I . Preoperative plasma levels of transforming growth factor beta(1) strongly predict clinical outcome in patients with bladder carcinoma. Cancer. 2001; 92(12):2985-92. DOI: 10.1002/1097-0142(20011215)92:12<2985::aid-cncr10175>3.0.co;2-5. View

13.

Siegel R, Naishadham D, Jemal A . Cancer statistics, 2013. CA Cancer J Clin. 2013; 63(1):11-30. DOI: 10.3322/caac.21166. View

14.

Qi W, Gao S, Wang Z . Transcriptional regulation of the TGF-beta1 promoter by androgen receptor. Biochem J. 2008; 416(3):453-62. DOI: 10.1042/BJ20080651. View

15.

Han G, Lu S, Li A, He W, Corless C, Kulesz-Martin M . Distinct mechanisms of TGF-beta1-mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis. J Clin Invest. 2005; 115(7):1714-23. PMC: 1142114. DOI: 10.1172/JCI24399. View

16.

Zhu W, Cai M, Tong Z, Dong S, Mai S, Liao Y . Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition. Gut. 2011; 61(4):562-75. DOI: 10.1136/gutjnl-2011-300207. View

17.

Xie D, Ma N, Pan Z, Wu H, Liu Y, Wu G . Overexpression of EIF-5A2 is associated with metastasis of human colorectal carcinoma. Hum Pathol. 2007; 39(1):80-6. DOI: 10.1016/j.humpath.2007.05.011. View

18.

Stenzl A, Cowan N, De Santis M, Kuczyk M, Merseburger A, Ribal M . Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines. Eur Urol. 2011; 59(6):1009-18. DOI: 10.1016/j.eururo.2011.03.023. View

19.

Weigert C, Brodbeck K, Sawadogo M, Haring H, Schleicher E . Upstream stimulatory factor (USF) proteins induce human TGF-beta1 gene activation via the glucose-response element-1013/-1002 in mesangial cells: up-regulation of USF activity by the hexosamine biosynthetic pathway. J Biol Chem. 2004; 279(16):15908-15. DOI: 10.1074/jbc.M313524200. View

20.

Eder I, Stenzl A, Hobisch A, Cronauer M, Bartsch G, Klocker H . Expression of transforming growth factors beta-1, beta 2 and beta 3 in human bladder carcinomas. Br J Cancer. 1997; 75(12):1753-60. PMC: 2223615. DOI: 10.1038/bjc.1997.299. View