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Tissue stiffness contributes to YAP activation in bladder cancer patients undergoing transurethral resection.
Annals of the New York Academy of Sciences ( IF 4.295 ) Pub Date : 2020-05-19 , DOI: 10.1111/nyas.14358
Hadi Ghasemi,Seyed Habibollah Mousavibahar,Mohammad Hashemnia,Jamshid Karimi,Iraj Khodadadi,Fatemeh Mirzaei,Heidar Tavilani

Changes in the cellular microenvironment play a critical role in the development of bladder cancer (BC). Yes-associated protein (YAP), a central mediator of the Hippo pathway, functions as a nuclear sensor of mechanotransduction that can be induced by stiffness of the extracellular matrix (ECM), including stiffness resulting from surgical manipulations. We aimed to clarify the possible association between surgically-related ECM stiffness and YAP activation in BC patients. We compared 30 bladder cancer tissues with grade II (n = 15 recurrent and n = 15 newly diagnosed) with 30 adjacent healthy tissues. Atomic force microscopy showed that patients with recurrent BC had stiffer ECM than newly diagnosed patients (P < 0.05). Gene expression profiles showed that β1 integrin (ITGB1), focal adhesion kinase (FAK), CDC42, and YAP were upregulated in cancerous tissues (P < 0.05); additionally, β1 integrin activation was confirmed using a specific antibody. Nuclear localization of YAP was higher in recurrent cancerous tissues compared with newly diagnosed and it was positively associated with higher stiffness (P < 0.05). Our results suggest that postsurgery-induced ECM stiffness can influence integrin-FAK-YAP activity and thereby YAP trafficking to the nucleus where it contributes to BC progression and relapse.
更新日期:2020-05-19

 

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