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

• DOI: 10.1242/jcs.177592
• Publication Date: 2016-02-13T12:05:13Z
• Authors: Michaela-Rosemari...; Madis Jakobson; Georgina P. Colo; Emanuel Rognoni; Maili Jakobson; Christian Kupatt; Guido Posern; Reinhard Fässler
• Keywords: ISG15

ABSTRACT Integrin-mediated activation of small GTPases induces the polymerisation G-actin into various actin structures and release transcriptional co-activator MRTF from G-actin. Here we report that pan-integrin-null fibroblasts seeded on fibronectin expressing β1- and/or αV-class integrin contained different pools, nuclear MRTF-A (also known as MKL1 or MAL) levels MRTF-A–SRF activities. The activities were highest in cells both classes, lower β1 integrins lowest αV integrins. Quantitative proteomics transcriptomics analyses linked differential to expression ubiquitin-like modifier interferon-stimulated gene 15 (ISG15), which is modify focal adhesion cytoskeletal proteins. malignant breast cancer cell line MDA-MB-231 expressed high integrins, ISG15 ISGylated proteins, promoted invasive properties, whereas non-invasive MDA-MB-468 MCF-7 lines low Our findings suggest integrin-adhesion-induced constitute a newly discovered signalling circuit promotes migration invasion.