Format

Send to

Choose Destination

RETRACTED ARTICLE

See: Retraction Notice

Cell. 2016 Dec 1;167(6):1571-1585.e18. doi: 10.1016/j.cell.2016.10.023. Epub 2016 Nov 10.

FMN2 Makes Perinuclear Actin to Protect Nuclei during Confined Migration and Promote Metastasis.

Author information

1
Cell Biology and Physiology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
2
Cell Biology and Physiology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; Institut Curie, CNRS UMR 144, 26 rue d'Ulm, 75005 Paris, France.
3
Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
4
Cell Biology and Physiology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; Magnet Lab, Florida State University, Tallahassee, FL 32306, USA.
5
Magnet Lab, Florida State University, Tallahassee, FL 32306, USA.
6
Institut Curie, CNRS UMR 144, 26 rue d'Ulm, 75005 Paris, France.
7
Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
8
Cell Biology and Physiology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: watermancm@nhlbi.nih.gov.

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.

KEYWORDS:

DNA damage; actin; cell migration; confined migration; focal adhesion; formin; melanoma; metastasis; stress fiber; ventral actin bundle

Comment in

Comment on

PMID:
27839864
PMCID:
PMC5135586
DOI:
10.1016/j.cell.2016.10.023
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center