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  Integrins synergise to induce expression of the MRTF-A-SRF target gene ISG15 for promoting cancer cell invasion

Hermann, M.-R., Jakobson, M., Colo, G. P., Rognoni, E., Jakobson, M., Kupatt, C., et al. (2016). Integrins synergise to induce expression of the MRTF-A-SRF target gene ISG15 for promoting cancer cell invasion. JOURNAL OF CELL SCIENCE, 129(7), 1391-1403. doi:10.1242/jcs.177592.

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 Creators:
Hermann, Michaela-Rosemarie1, Author              
Jakobson, Madis1, Author              
Colo, Georgina P.1, Author              
Rognoni, Emanuel1, Author              
Jakobson, Maili1, Author              
Kupatt, Christian2, Author
Posern, Guido2, Author
Fässler, Reinhard1, Author              
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              
2external, ou_persistent22              

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Free keywords: SERUM-RESPONSE FACTOR; UBIQUITIN-LIKE PROTEINS; ACTIN DYNAMICS; TUMOR-CELLS; TRANSCRIPTION; ACTIVATION; MIGRATION; CONJUGATION; PATHWAY; IDENTIFICATIONCell migration; Integrin; ISG15; MRTF-A; SRF;
 Abstract: Integrin-mediated activation of small GTPases induces the polymerisation of G-actin into various actin structures and the release of the transcriptional co-activator MRTF from G-actin. Here we report that pan-integrin-null fibroblasts seeded on fibronectin and expressing beta 1- and/or alpha V-class integrin contained different G-actin pools, nuclear MRTF-A (also known as MKL1 or MAL) levels and MRTF-A-SRF activities. The nuclear MRTF-A levels and activities were highest in cells expressing both integrin classes, lower in cells expressing beta 1 integrins and lowest in cells expressing the alpha V integrins. Quantitative proteomics and transcriptomics analyses linked the differential MRTF-A activities to the expression of the ubiquitin-like modifier interferon-stimulated gene 15 (ISG15), which is known to modify focal adhesion and cytoskeletal proteins. The malignant breast cancer cell line MDA-MB-231 expressed high levels of beta 1 integrins, ISG15 and ISGylated proteins, which promoted invasive properties, whereas non-invasive MDA-MB-468 and MCF-7 cell lines expressed low levels of beta 1 integrins, ISG15 and ISGylated proteins. Our findings suggest that integrin-adhesion-induced MRTF-A-SRF activation and ISG15 expression constitute a newly discovered signalling circuit that promotes cell migration and invasion.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: Internal
 Identifiers: ISI: 000374949100011
DOI: 10.1242/jcs.177592
 Degree: -

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Title: JOURNAL OF CELL SCIENCE
Source Genre: Journal
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Publ. Info: BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND : COMPANY OF BIOLOGISTS LTD
Pages: - Volume / Issue: 129 (7) Sequence Number: - Start / End Page: 1391 - 1403 Identifier: ISSN: 0021-9533