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

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.

SUBMITTER: Gao Y

PROVIDER: S-EPMC6643140 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Gao Yanjun Y Liu Shanhui S Guo Qi Q Zhang Su S Zhao Youli Y Wang Hanzhang H Li Tianbao T Gong Yuwen Y Wang Yuhan Y Zhang Tao T Dong Zhilong Z Bacich Dean D Chowdhury Wasim H WH Rodriguez Ronald R Wang Zhiping Z

International journal of biological sciences 20190602 7

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 ...[more]

PMID: 31337978

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Project description:BackgroundBladder cancer (BLCA) is one of the most common malignancies worldwide. One of the main reasons for the unsatisfactory management of BLCA is the complex molecular biological mechanism. Annexin A1 (ANXA1), a Ca2+-regulated phospholipid-binding protein, has been demonstrated to be implicated in the progression and prognosis of many cancers. However, the expression pattern, biological function and mechanism of ANXA1 in BLCA remain unclear.MethodsThe clinical relevance of ANXA1 in BLCA was investigated by bioinformatics analysis based on TCGA and GEO datasets. Immunohistochemical (IHC) analysis was performed to detect the expression of ANXA1 in BLCA tissues, and the relationships between ANXA1 and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to study the biological functions of ANXA1 in BLCA. Finally, the potential mechanism of ANXA1 in BLCA was explored by bioinformatics analysis and verified by in vitro and in vivo experiments.ResultsBioinformatics and IHC analyses indicated that a high expression level of ANXA1 was strongly associated with the progression and poor prognosis of patients with BLCA. Functional studies demonstrated that ANXA1 silencing inhibited the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of BLCA cells in vitro, and suppressed the growth of xenografted bladder tumors in vivo. Mechanistically, loss of ANXA1 decreased the expression and phosphorylation level of EGFR and the activation of downstream signaling pathways. In addition, knockdown of ANXA1 accelerated ubiquitination and degradation of P-EGFR to downregulate the activation of EGFR signaling.ConclusionsThese findings indicate that ANXA1 is a reliable clinical predictor for the prognosis of BLCA and promotes proliferation and migration by activating EGFR signaling in BLCA. Therefore, ANXA1 may be a promising biomarker for the prognosis of patients with BLCA, thus shedding light on precise and personalized therapy for BLCA in the future.

Dataset Information

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

Publications

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

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