TACC3 Transcriptionally Upregulates E2F1 to Promote Cell Growth and Confer Sensitivity to Cisplatin in Bladder Cancer

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2018 Jan 24

PMID 29358577

Citations 11

Authors

Zhi-Rui Lin

Meng-Yao Wang

Shi-Yang He

Zhi-Ming Cai

Wei-Ren Huang

Affiliations

Soon will be listed here.

Abstract

Accumulating evidence has shown that transforming acidic coiled-coil 3 (TACC3) is deregulated in a broad spectrum of cancers. In the present study, we reported that TACC3 was markedly elevated in bladder cancer, especially in muscle-invasive bladder cancers (MIBCs). The upregulation of TACC3 was positively associated with tumor invasiveness, grade, T stage, and progression in patients with bladder cancer. Furthermore, a Kaplan-Meier survival analysis showed that patients with bladder cancer whose tumors had high TACC3 expression experienced a dismal prognosis compared with patients whose tumors had low TACC3 expression. Functional studies have found that TACC3 is a prerequisite for the development of malignant characteristics of bladder cancer cells, including cell proliferation and invasion. Moreover, TACC3 promoted G1/S transition, which was mediated via activation of the transcription of E2F1, eventually enhancing cell proliferation. Notably, the overexpression of TACC3 or E2F1 indicates a high sensitivity to cisplatin. Taken together, these findings define a tumor-supportive role for TACC3, which may also serve as a prognostic and therapeutic indicator in bladder cancers.

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References

Ohtani K, Tsujimoto A, Ikeda M, Nakamura M . Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F. Oncogene. 1998; 17(14):1777-85. DOI: 10.1038/sj.onc.1202105. View

Yuan L, Liu Z, Lin Z, Xu L, Zhong Q, Zeng M . Recurrent FGFR3-TACC3 fusion gene in nasopharyngeal carcinoma. Cancer Biol Ther. 2014; 15(12):1613-21. PMC: 4622012. DOI: 10.4161/15384047.2014.961874. View

Schneider L, Essmann F, Kletke A, Rio P, Hanenberg H, Wetzel W . The transforming acidic coiled coil 3 protein is essential for spindle-dependent chromosome alignment and mitotic survival. J Biol Chem. 2007; 282(40):29273-83. DOI: 10.1074/jbc.M704151200. View

Tomlinson D, Baldo O, Harnden P, Knowles M . FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer. J Pathol. 2007; 213(1):91-8. PMC: 2443273. DOI: 10.1002/path.2207. View

Partch C, Gardner K . Coactivators necessary for transcriptional output of the hypoxia inducible factor, HIF, are directly recruited by ARNT PAS-B. Proc Natl Acad Sci U S A. 2011; 108(19):7739-44. PMC: 3093465. DOI: 10.1073/pnas.1101357108. View

Williams S, Hurst C, Knowles M . Oncogenic FGFR3 gene fusions in bladder cancer. Hum Mol Genet. 2012; 22(4):795-803. PMC: 3554204. DOI: 10.1093/hmg/dds486. View

Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F . Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends. Eur Urol. 2016; 71(1):96-108. DOI: 10.1016/j.eururo.2016.06.010. View

Shah J, McConkey D, Dinney C . New strategies in muscle-invasive bladder cancer: on the road to personalized medicine. Clin Cancer Res. 2011; 17(9):2608-12. DOI: 10.1158/1078-0432.CCR-10-2770. View

Zhou D, Wang H, Zhou Z, Zhang Y, Zhong Q, Xu L . TACC3 promotes stemness and is a potential therapeutic target in hepatocellular carcinoma. Oncotarget. 2015; 6(27):24163-77. PMC: 4695177. DOI: 10.18632/oncotarget.4643. View

10.

Ha G, Kim J, Breuer E, Breuer E . TACC3 is essential for EGF-mediated EMT in cervical cancer. PLoS One. 2013; 8(8):e70353. PMC: 3731346. DOI: 10.1371/journal.pone.0070353. View

11.

Knowles M, Hurst C . Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat Rev Cancer. 2014; 15(1):25-41. DOI: 10.1038/nrc3817. View

12.

Li Q, Ye L, Guo W, Wang M, Huang S, Peng X . Overexpression of TACC3 is correlated with tumor aggressiveness and poor prognosis in prostate cancer. Biochem Biophys Res Commun. 2017; 486(4):872-878. DOI: 10.1016/j.bbrc.2017.03.090. View

13.

Real P, Sanz C, Gutierrez O, Pipaon C, Zubiaga A, Fernandez-Luna J . Transcriptional activation of the proapoptotic bik gene by E2F proteins in cancer cells. FEBS Lett. 2006; 580(25):5905-9. DOI: 10.1016/j.febslet.2006.08.088. View

14.

Dyrskjot L, Kruhoffer M, Thykjaer T, Marcussen N, Jensen J, Moller K . Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification. Cancer Res. 2004; 64(11):4040-8. DOI: 10.1158/0008-5472.CAN-03-3620. View

15.

Kim W, Kim E, Kim S, Kim Y, Ha Y, Jeong P . Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer. Mol Cancer. 2010; 9:3. PMC: 2821358. DOI: 10.1186/1476-4598-9-3. View

16.

Araki K, Nakajima Y, Eto K, Ikeda M . Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter. Oncogene. 2003; 22(48):7632-41. DOI: 10.1038/sj.onc.1206840. View

17.

Riester M, Taylor J, Feifer A, Koppie T, Rosenberg J, Downey R . Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk bladder cancer. Clin Cancer Res. 2012; 18(5):1323-33. PMC: 3569085. DOI: 10.1158/1078-0432.CCR-11-2271. View

18.

Wingender E, Chen X, Hehl R, Karas H, Liebich I, Matys V . TRANSFAC: an integrated system for gene expression regulation. Nucleic Acids Res. 1999; 28(1):316-9. PMC: 102445. DOI: 10.1093/nar/28.1.316. View

19.

Guo G, Sun X, Chen C, Wu S, Huang P, Li Z . Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation. Nat Genet. 2013; 45(12):1459-63. PMC: 7512009. DOI: 10.1038/ng.2798. View

20.

Vigo E, Muller H, Prosperini E, Hateboer G, Cartwright P, Moroni M . CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase. Mol Cell Biol. 1999; 19(9):6379-95. PMC: 84608. DOI: 10.1128/MCB.19.9.6379. View