ITGB1-dependent upregulation of Caveolin-1 switches TGFβ signalling from tumour-suppressive to oncogenic in prostate cancer.

Abstract	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 TGFβ 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 TGFβ signalling and beta1 integrins as potential therapeutic targets in PCa over-expressing CAV1, and contributes to better understand the paradoxical dual role of TGFβ in tumour biology.
Authors	Teijo Pellinen, Sami Blom, Sara Sánchez, Katja Välimäki, John-Patrick Mpindi, Hind Azegrouz, Raffaele Strippoli, Raquel Nieto, Mariano Vitón, Irene Palacios, Riku Turkki, Yinhai Wang, Miguel Sánchez-Alvarez, Stig Nordling, Anna Bützow, Tuomas Mirtti, Antti Rannikko, María C Montoya, Olli Kallioniemi, Miguel A Del Pozo
Journal	Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 2338 (02 05 2018) ISSN: 2045-2322 [Electronic] England
PMID	29402961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing CAV1 protein, human Caveolin 1 ITGB1BP1 protein, human Intracellular Signaling Peptides and Proteins Membrane Proteins TGFB1 protein, human Transforming Growth Factor beta1
Topics	Adaptor Proteins, Signal Transducing Caveolin 1 (metabolism) Cell Line, Tumor Gene Expression Regulation, Neoplastic Humans Intracellular Signaling Peptides and Proteins (metabolism) Male Membrane Proteins (metabolism) Oncogenes Phenotype Prostatic Neoplasms (genetics, metabolism) Signal Transduction Transforming Growth Factor beta1 (metabolism) Up-Regulation

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