Glucocorticoid receptor signalling activates YAP in breast cancer
| Autor: | Mattia Forcato, Antonio Rosato, Miguel Mano, Rebecca Bertolio, Elisa Cappuzzello, Naomi Ruggeri, Alessandro Zannini, Carolina Marotta, Eleonora Ingallina, Carmelo Neri, Silvio Bicciato, Giovanni Sorrentino, Giannino Del Sal |
|---|---|
| Přispěvatelé: | Sorrentino, G., Ruggeri, N., Zannini, A., Ingallina, E., Bertolio, R., Marotta, C., Neri, C., Cappuzzello, E., Forcato, M., Rosato, A., Mano, M., Bicciato, S., Del Sal, G. |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetics and Molecular Biology (all) General Physics and Astronomy medicine.disease_cause Biochemistry Mice Glucocorticoid receptor Regulation of gene expression Multidisciplinary glucocorticoids Chemistry (all) 3. Good health Gene Expression Regulation Neoplastic Female Yap Signal transduction Signal Transduction medicine.medical_specialty Science Breast Neoplasms Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Physics and Astronomy (all) Receptors Glucocorticoid breast cancer Cancer stem cell Internal medicine Cell Line Tumor medicine Animals Humans Transcription factor Adaptor Proteins Signal Transducing Hippo signaling pathway Cell growth YAP-Signaling Proteins General Chemistry Neoplasms Experimental Phosphoproteins Mice Inbred C57BL 030104 developmental biology Endocrinology Cancer research glucocorticoid Biochemistry Genetics and Molecular Biology (all) Carcinogenesis Transcription Factors |
| Zdroj: | Nature Communications Nature Communications, Vol 8, Iss 1, Pp 1-14 (2017) |
| Popis: | 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. Activation of YAP contributes to tumorigenesis in several tissues. Here, the authors show that in breast cancer cells glucocorticoids induce expression of fibronectin that in turn activates focal adhesion kinase/Src signalling to promote YAP nuclear translocation and transcriptional activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|