Newman, Daniel, Young, Lorna E., Waring, Thomas, Brown, Louise, Wolanska, Katarzyna I., MacDonald, Ewan, Charles-Orszag, Arthur, Goult, Benjamin T, Caswell, Patrick T., Sakuma, Tetsushi, and others. (2023) 3D matrix adhesion feedback controls nuclear force coupling to drive invasive cell migration. Cell Reports, 42 (12). Article Number 113554. ISSN 2211-1247. (doi:10.1016/j.celrep.2023.113554) (KAR id:104307)
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| Official URL: https://doi.org/10.1016/j.celrep.2023.113554 |
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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. bPix 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-bPix 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 |
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| DOI/Identification number: | 10.1016/j.celrep.2023.113554 |
| Uncontrolled keywords: | invasion; adhesion; nuclear force coupling; integrin-based adhesion complexes; polarity; protrusion; myosin; actin; contractility |
| Subjects: | Q Science > QH Natural history > QH581.2 Cell Biology |
| Divisions: | Divisions > Division of Natural Sciences > Biosciences |
| Funders: |
University of Kent (https://ror.org/00xkeyj56)
Biotechnology and Biological Sciences Research Council (https://ror.org/00cwqg982) |
| Depositing User: | Ben Goult |
| Date Deposited: | 15 Dec 2023 16:47 UTC |
| Last Modified: | 13 Feb 2024 10:15 UTC |
| Resource URI: | https://kar.kent.ac.uk/id/eprint/104307 (The current URI for this page, for reference purposes) |
University of Kent Author Information
Goult, Benjamin T.
| Creator's ORCID: |
 https://orcid.org/0000-0002-3438-2807
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