Newman, Daniel, Young, Lorna E 
ORCID: 0000-0003-3521-9697, Waring, Thomas ORCID: 0000-0002-3280-8886, Brown, Louise, Wolanska, Katarzyna I, MacDonald, Ewan, Charles-Orszag, Arthur, Goult, Benjamin T, Caswell, Patrick T, Sakuma, Tetsushi et al (show 4 more authors)
(2023)
3D matrix adhesion feedback controls nuclear force coupling to drive invasive cell migration.
Cell reports, 42 (12).
113554-.
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CELL-REPORTS-D-22-03117_accepted manuscript.pdf - Author Accepted Manuscript Download (15MB) | Preview |
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Extracellular Matrix, Myosins, Actomyosin, Cell Adhesion, Cell Movement, Feedback, Actin Cytoskeleton |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology Faculty of Health and Life Sciences > Tech, Infrastructure and Environmental Directorate |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 14 Dec 2023 15:12 |
| Last Modified: | 16 Feb 2024 15:52 |
| DOI: | 10.1016/j.celrep.2023.113554 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3177393 |
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