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https://hdl.handle.net/10316/108280
Título: | Glucocorticoid receptor signalling activates YAP in breast cancer | Autor: | Sorrentino, Giovanni Ruggeri, Naomi Zannini, Alessandro Ingallina, Eleonora Bertolio, Rebecca Marotta, Carolina Neri, Carmelo Cappuzzello, Elisa Forcato, Mattia Rosato, Antonio Mano, Miguel Bicciato, Silvio Del Sal, Giannino |
Data: | 19-Jan-2017 | Projeto: | grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC) and AIRC Special Program Molecular Clinical Oncology ‘5 per mille’ (Grant no. 10016) and Italian Ministry of Health, to G.D.S.,S.B. and A.R. M.M. is supported by the FIRB RBAP11Z4Z9 project from the Italian Ministry of Education and the FCT Investigator Programme IF/00694/2013 from the Portuguese Foundation for Science and Technology (FCT), Portugal M.F. is supported by FIRB RBAP11T3WB and ERC grant no. 670126 Denovostem. |
Título da revista, periódico, livro ou evento: | Nature Communications | Volume: | 8 | Número: | 1 | Resumo: | The Hippo pathway is an oncosuppressor signalling cascade that plays a major role in the control of cell growth, tissue homoeostasis and organ size. Dysregulation of the Hippo pathway leads to aberrant activation of the transcription co-activator YAP (Yes-associated protein) that contributes to tumorigenesis in several tissues. Here we identify glucocorticoids (GCs) as hormonal activators of YAP. Stimulation of glucocorticoid receptor (GR) leads to increase of YAP protein levels, nuclear accumulation and transcriptional activity in vitro and in vivo. Mechanistically, we find that GCs increase expression and deposition of fibronectin leading to the focal adhesion-Src pathway stimulation, cytoskeleton-dependent YAP activation and expansion of chemoresistant cancer stem cells. GR activation correlates with YAP activity in human breast cancer and predicts bad prognosis in the basal-like subtype. Our results unveil a novel mechanism of YAP activation in cancer and open the possibility to target GR to prevent cancer stem cells self-renewal and chemoresistance. | URI: | https://hdl.handle.net/10316/108280 | ISSN: | 2041-1723 | DOI: | 10.1038/ncomms14073 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Glucocorticoid-receptor-signalling-activates-YAP-in-breast-cancerNature-Communications.pdf | 1.91 MB | Adobe PDF | Ver/Abrir |
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