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Yes-associated protein 1 promotes bladder cancer invasion by regulating epithelial-mesenchymal transition.

ABSTRACT: PURPOSE:To investigate the expression of Yes-associated protein 1 (YAP1) in bladder cancer, and to study its role in regulating epithelial-mesenchymal transition in bladder cancer cells. MATERIAL AND METHODS:The expression of YAP1, vimentin, and E-cadherin was detected by immunohistochemistry in bladder cancer and para-carcinoma tissues. The relation between expression levels and overall survival of patients was evaluated by Kaplan-Meier estimates. Furthermore, YAP1 expression was knocked down in T24 and UMUC3 bladder cancer through transfection with YAP1-targeted small interfering RNA (siRNA), and the impact on invasiveness and epithelial-mesenchymal transition was detected. RESULTS:Expression levels of YAP1 were higher in bladder cancer tissues, and increased YAP1 expression significantly correlated with poor patient outcomes and poor overall survival in bladder cancer patients. Furthermore, YAP1 siRNA significantly attenuated the invasion of bladder cancer cells and could reverse their epithelial-mesenchymal transition. CONCLUSION:YAP1 appears to play an important role in bladder cancer progression and is highlighted as a novel potential therapeutic target.

SUBMITTER: Chen X

PROVIDER: S-EPMC6945140 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Yes-associated protein 1 promotes bladder cancer invasion by regulating epithelial-mesenchymal transition.

Chen Xingxing X Li Shi S Yu Zhe Z Tan Wanlong W

International journal of clinical and experimental pathology 20190301 3

<h4>Purpose</h4>To investigate the expression of Yes-associated protein 1 (YAP1) in bladder cancer, and to study its role in regulating epithelial-mesenchymal transition in bladder cancer cells.<h4>Material and methods</h4>The expression of YAP1, vimentin, and E-cadherin was detected by immunohistochemistry in bladder cancer and para-carcinoma tissues. The relation between expression levels and overall survival of patients was evaluated by Kaplan-Meier estimates. Furthermore, YAP1 expression was ...[more]

PMID: 31933921

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Project description:BackgroundMetastatic bladder cancer (BLCA) is a lethal disease with an unmet need for study. Transgelin (TAGLN) is an actin-binding protein that affects the dynamics of the actin cytoskeleton indicating its robust potential as a metastasis initiator. Here, we sought to explore the expression pattern of TAGLN and elucidate its specific functioning and mechanisms in BLCA.MethodsA comprehensive assessment of TAGLN expression in BLCA was performed in three cohorts with a total of 847 patients. The potential effects of TAGLN on BLCA were further determined using clinical genomic analyses that guided the subsequent functional and mechanistic studies. In vitro migration, invasion assays and in vivo metastatic mouse model were performed to explore the biological functions of TAGLN in BLCA cells. Immunofluorescence, western blot and correlation analysis were used to investigate the molecular mechanisms of TAGLN.FindingsTAGLN was highly expressed in BLCA and correlated with advanced prognostic features. TAGLN promoted cell colony formation and cell migration and invasion both in vitro and in vivo by inducing invadopodia formation and epithelial-mesenchymal transition, during which a significant correlation between TAGLN and Slug was observed. The progression-dependent correlation between TGF-β and TAGLN was analysed at both the cellular and tissue levels, while TGF-β-mediated migration was abolished by the suppression of TAGLN.InterpretationOverall, TAGLN is a promising novel prognosis biomarker of BLCA, and its metastatic mechanisms indicate that TAGLN may represent a novel target agent that can be utilized for the clinical management of invasive and metastatic BLCA. FUND: This work was supported by the National Natural Science Foundation of China [81772703, 81672546, 81602253]; the Natural Science Foundation of Beijing [71772219, 7152146]. and Innovative Fund for Doctoral Students of Peking University Health Science Center (BUM2018BSS002). Funders had no role in the design of the study, data collection, data analysis, interpretation, or the writing of this report.

Dataset Information

Yes-associated protein 1 promotes bladder cancer invasion by regulating epithelial-mesenchymal transition.

Publications

Yes-associated protein 1 promotes bladder cancer invasion by regulating epithelial-mesenchymal transition.

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