| Literature DB >> 27839864 |
Colleen T Skau1, Robert S Fischer1, Pinar Gurel1, Hawa Racine Thiam2, Anthony Tubbs3, Michelle A Baird4, Michael W Davidson5, Matthieu Piel6, Gregory M Alushin1, Andre Nussenzweig3, Patricia S Steeg7, Clare M Waterman8.
Abstract
Cell migration in confined 3D tissue microenvironments is critical for both normal physiological functions and dissemination of tumor cells. We discovered a cytoskeletal structure that prevents damage to the nucleus during migration in confined microenvironments. The formin-family actin filament nucleator FMN2 associates with and generates a perinuclear actin/focal adhesion (FA) system that is distinct from previously characterized actin/FA structures. This system controls nuclear shape and positioning in cells migrating on 2D surfaces. In confined 3D microenvironments, FMN2 promotes cell survival by limiting nuclear envelope damage and DNA double-strand breaks. We found that FMN2 is upregulated in human melanomas and showed that disruption of FMN2 in mouse melanoma cells inhibits their extravasation and metastasis to the lung. Our results indicate a critical role for FMN2 in generating a perinuclear actin/FA system that protects the nucleus and DNA from damage to promote cell survival during confined migration and thus promote cancer metastasis. Published by Elsevier Inc.Entities:
Keywords: DNA damage; actin; cell migration; confined migration; focal adhesion; formin; melanoma; metastasis; stress fiber; ventral actin bundle
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Year: 2016 PMID： 27839864 PMCID： PMC5135586 DOI： 10.1016/j.cell.2016.10.023
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582