Tissue stiffness contributes to YAP activation in bladder cancer patients undergoing transurethral resection.
Ann N Y Acad Sci
; 1473(1): 48-61, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32428277
ABSTRACT
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 ß1 integrin (ITGB1), focal adhesion kinase (FAK), CDC42, and YAP were upregulated in cancerous tissues (P < 0.05); additionally, ß1 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.
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MEDLINE
Assunto principal:
Fatores de Transcrição
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Neoplasias da Bexiga Urinária
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Biomarcadores Tumorais
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Mecanotransdução Celular
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Proteínas Adaptadoras de Transdução de Sinal
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Microambiente Tumoral
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article