Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6690
ITGB1-dependent upregulation of Caveolin-1 switches TGF beta signalling from tumour-suppressive to oncogenic in prostate cancer
Pellinen, Teijo CNIC | Blom, Sami | Sanchez, Sara CNIC | Valimaki, Katja | Mpindi, John-Patrick | Azegrouz, Hind CNIC | Strippoli, Raffaele CNIC | Nieto-Arellano, Rocio CNIC | Viton, Mariano CNIC | Palacios, Irene CNIC | Turkki, Riku | Wang, Yinhai | Sanchez-Alvarez, Miguel CNIC | Nordling, Stig | Butzow, Anna | Mirtti, Tuomas | Rannikko, Antti | Montoya, María CNIC | Kallioniemi, Olli | del Pozo, Miguel Angel CNIC
Sci Rep. 2018; 8(1):2338
Caveolin-1 (CAV1) is over-expressed in prostate cancer (PCa) and is associated with adverse prognosis, but the molecular mechanisms linking CAV1 expression to disease progression are poorly understood. Extensive gene expression correlation analysis, quantitative multiplex imaging of clinical samples, and analysis of the CAV1-dependent transcriptome, supported that CAV1 re-programmes TGF beta signalling from tumour suppressive to oncogenic (i.e. induction of SLUG, PAI-1 and suppression of CDH1, DSP, CDKN1A). Supporting such a role, CAV1 knockdown led to growth arrest and inhibition of cell invasion in prostate cancer cell lines. Rationalized RNAi screening and high-content microscopy in search for CAV1 upstream regulators revealed integrin beta1 (ITGB1) and integrin associated proteins as CAV1 regulators. Our work suggests TGF beta signalling and beta1 integrins as potential therapeutic targets in PCa over-expressing CAV1, and contributes to better understand the paradoxical dual role of TGF beta in tumour biology.