3D matrix adhesion feedback controls nuclear force coupling to drive invasive cell migration.

Published version
Repository DOI

Type
Article
Change log
Authors
Newman, Daniel 
Young, Lorna E 
Waring, Thomas 
Brown, Louise 
Wolanska, Katarzyna I 
Abstract

Cell invasion is a multi-step process, initiated by the acquisition of a migratory phenotype and the ability to move through complex 3D extracellular environments. We determine the composition of cell-matrix adhesion complexes of invasive breast cancer cells in 3D matrices and identify an interaction complex required for invasive migration. βPix and myosin18A (Myo18A) drive polarized recruitment of non-muscle myosin 2A (NM2A) to adhesion complexes at the tips of protrusions. Actomyosin force engagement then displaces the Git1-βPix complex from paxillin, establishing a feedback loop for adhesion maturation. We observe active force transmission to the nucleus during invasive migration that is needed to pull the nucleus forward. The recruitment of NM2A to adhesions creates a non-muscle myosin isoform gradient, which extends from the protrusion to the nucleus. We postulate that this gradient facilitates coupling of cell-matrix interactions at the protrusive cell front with nuclear movement, enabling effective invasive migration and front-rear cell polarity.

Description
Keywords
CP: Cell biology, actin, adhesion, contractility, integrin-based adhesion complexes, invasion, myosin, nuclear force coupling, polarity, protrusion, Feedback, Cell Movement, Actomyosin, Actin Cytoskeleton, Myosins, Cell Adhesion, Extracellular Matrix
Journal Title
Cell Rep
Conference Name
Journal ISSN
2211-1247
2211-1247
Volume Title
42
Publisher
Elsevier BV
Sponsorship
Breast Cancer Now (2014MayPR292)
Cancer Research UK (DRCRPG-Nov22/100017)