Integrins synergize to induce expression of the MRTF-A/SRF target gene ISG15 for promoting cancer cell invasion
| Autor: | Madis Jakobson, Guido Posern, Maili Jakobson, Georgina P. Colo, Reinhard Fässler, Emanuel Rognoni, Christian Kupatt, Michaela-Rosemarie Hermann |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Integrin Breast Neoplasms Biology Focal adhesion 03 medical and health sciences Cell Movement Cell Line Tumor Cell Adhesion Humans Neoplasm Invasiveness Neoplasm Metastasis RNA Small Interfering Cell adhesion Cytoskeleton Ubiquitins Focal Adhesions Integrin beta1 Cell migration Cell Biology Integrin alphaV Actins Cell biology Fibronectin 030104 developmental biology Cancer cell MCF-7 Cells Trans-Activators biology.protein Cancer research Cytokines RNA Interference |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | 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 β1- and/or αV-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 β1 integrins and lowest in cells expressing the αV 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 β1 integrins, ISG15 and ISGylated proteins, which promoted invasive properties, whereas non-invasive MDA-MB-468 and MCF-7 cell lines expressed low levels of β1 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. |
| Databáze: | OpenAIRE |
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