Int J Biol Sci 2019; 15(7):1488-1499. doi:10.7150/ijbs.32718

Research Paper

Increased expression of TRIP13 drives the tumorigenesis of bladder cancer in association with the EGFR signaling pathway

Yanjun Gao1#, Shanhui Liu1#, Qi Guo1, Su Zhang1, Youli Zhao1, Hanzhang Wang2, Tianbao Li3, Yuwen Gong1, Yuhan Wang1, Tao Zhang1, Zhilong Dong1✉, Dean Bacich2, Wasim H. Chowdhury2, Ronald Rodriguez2, Zhiping Wang1✉

1. Department of Urology, The Second Hospital of Lanzhou University, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou 730000, China
2. Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
3. Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA
#These authors contributed to the work equally.

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Citation:
Gao Y, Liu S, Guo Q, Zhang S, Zhao Y, Wang H, Li T, Gong Y, Wang Y, Zhang T, Dong Z, Bacich D, Chowdhury WH, Rodriguez R, Wang Z. Increased expression of TRIP13 drives the tumorigenesis of bladder cancer in association with the EGFR signaling pathway. Int J Biol Sci 2019; 15(7):1488-1499. doi:10.7150/ijbs.32718. Available from http://www.ijbs.com/v15p1488.htm

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Abstract

Thyroid hormone receptor interactor 13 (TRIP13) is a crucial regulator of the spindle apparatus checkpoint and double-stranded break repair. The abnormal expression of TRIP13 was recently found in several human cancers, whereas the role of TRIP13 in the development of bladder cancer (BCa) has not been fully elucidated. Here, we reported that TRIP13 expression was elevated in BCa tissues compared with normal bladder tissues. Notably, the increased expression of TRIP13 was correlated with advanced tumor stage, lymph node metastasis, distant metastasis and reduced survival in BCa patients. Knockdown of TRIP13 in bladder cancer cells suppressed proliferation, induced cell cycle arrest, promoted apoptosis, and impaired cell motility, ultimately inhibiting tumor xenograft growth. Mechanistic investigations revealed that TRIP13 directly bound to epidermal growth factor receptor (EGFR), modulating the EGFR signaling pathway. Furthermore, TRIP13 expression was positively correlated with EGFR expression in BCa specimens, and the high expression of both TRIP13 and EGFR predicted poor survival. Overall, our results underscore the crucial role of TRIP13 in the tumorigenesis of BCa and provide a novel biomarker and therapeutic target for BCa treatment.

Keywords: TRIP13, Tumorigenesis, Bladder cancer, EGFR