ITGB1-dependent upregulation of Caveolin-1 switches TGFβ signalling from tumour-suppressive to oncogenic in prostate cancer
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...
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| Veröffentlicht in: | Scientific reports 2018-02, Vol.8 (1), p.2338-14, Article 2338 |
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| creator | Pellinen, Teijo Blom, Sami Sánchez, Sara Välimäki, Katja Mpindi, John-Patrick Azegrouz, Hind Strippoli, Raffaele Nieto, Raquel Vitón, Mariano Palacios, Irene Turkki, Riku Wang, Yinhai Sánchez-Alvarez, Miguel Nordling, Stig Bützow, Anna Mirtti, Tuomas Rannikko, Antti Montoya, María C. Kallioniemi, Olli del Pozo, Miguel A. |
| description | 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. |
| doi_str_mv | 10.1038/s41598-018-20161-2 |
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-20161-2</identifier><identifier>PMID: 29402961</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/106 ; 13/51 ; 14 ; 14/1 ; 14/63 ; 38 ; 38/39 ; 38/89 ; 45/47 ; 631/553/2711 ; 631/67/1857 ; 631/80/304 ; 692/4017 ; 692/4025/1752 ; Adaptor Proteins, Signal Transducing ; Caveolin ; Caveolin 1 - metabolism ; Caveolin-1 ; Cell Line, Tumor ; Correlation analysis ; E-cadherin ; Gene expression ; Gene Expression Regulation, Neoplastic ; Humanities and Social Sciences ; Humans ; Integrins ; Intracellular Signaling Peptides and Proteins - metabolism ; Male ; Membrane Proteins - metabolism ; Molecular modelling ; multidisciplinary ; Oncogenes ; Phenotype ; Prostate cancer ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - metabolism ; RNA-mediated interference ; Science ; Science (multidisciplinary) ; Signal Transduction ; Transforming Growth Factor beta1 - metabolism ; Tumor cell lines ; Tumors ; Up-Regulation</subject><ispartof>Scientific reports, 2018-02, Vol.8 (1), p.2338-14, Article 2338</ispartof><rights>The Author(s) 2018</rights><rights>2018. 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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. 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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. 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| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; SWEPUB Freely available online; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
| subjects | 13 13/106 13/51 14 14/1 14/63 38 38/39 38/89 45/47 631/553/2711 631/67/1857 631/80/304 692/4017 692/4025/1752 Adaptor Proteins, Signal Transducing Caveolin Caveolin 1 - metabolism Caveolin-1 Cell Line, Tumor Correlation analysis E-cadherin Gene expression Gene Expression Regulation, Neoplastic Humanities and Social Sciences Humans Integrins Intracellular Signaling Peptides and Proteins - metabolism Male Membrane Proteins - metabolism Molecular modelling multidisciplinary Oncogenes Phenotype Prostate cancer Prostatic Neoplasms - genetics Prostatic Neoplasms - metabolism RNA-mediated interference Science Science (multidisciplinary) Signal Transduction Transforming Growth Factor beta1 - metabolism Tumor cell lines Tumors Up-Regulation |
| title | ITGB1-dependent upregulation of Caveolin-1 switches TGFβ signalling from tumour-suppressive to oncogenic in prostate cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T01%3A46%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=ITGB1-dependent%20upregulation%20of%20Caveolin-1%20switches%20TGF%CE%B2%20signalling%20from%20tumour-suppressive%20to%20oncogenic%20in%20prostate%20cancer&rft.jtitle=Scientific%20reports&rft.au=Pellinen,%20Teijo&rft.date=2018-02-05&rft.volume=8&rft.issue=1&rft.spage=2338&rft.epage=14&rft.pages=2338-14&rft.artnum=2338&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-018-20161-2&rft_dat=%3Cproquest_swepu%3E1995159368%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1994394810&rft_id=info:pmid/29402961&rfr_iscdi=true |