Journal
MATRIX BIOLOGY
Volume 93, Issue -, Pages 60-78Publisher
ELSEVIER
DOI: 10.1016/j.matbio.2020.05.005
Keywords
Collective cell migration; Epithelial-to-mesenchymal transition; Fibronectin; Inhibition of integrin function; Kindlin-2; Rho GTPases
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Funding
- Netherlands Organization for Scientific Research (ZonMW) [Veni 016.146.160]
- Dutch Thrombosis Foundation [TSN 2017-01]
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Collective cell behaviour during embryogenesis and tissue repair requires the coordination of intercellular junctions, cytoskeleton-dependent shape changes controlled by Rho GTPases, and integrin-dependent cell-matrix adhesion. Many different integrins are simultaneously expressed during wound healing, embryonic development, and sprouting angiogenesis, suggesting that there is extensive integrin/integrin cross-talk to regulate cell behaviour. Here, we show that fibronectin-binding beta 1 and beta 3 integrins do not act synergistically, but rather antagonize each other during collective cell processes in neuro-epithelial cells, placental trophoblasts, and endothelial cells. Reciprocal beta 1/beta 3 antagonism controls RhoA activity in a kindlin-2-dependent manner, balancing cell spreading, contractility, and intercellular adhesion. In this way, reciprocal beta 1/beta 3 antagonism controls cell cohesion and cellular plasticity to switch between extreme and opposing states, including epithelial versus mesenchymal-like phenotypes and collective versus individual cell migration. We propose that integrin/integrin antagonism is a universal mechanism to effectuate social cellular interactions, important for tissue morphogenesis, endothelial barrier function, trophoblast invasion, and sprouting angiogenesis. (C) 2020 Published by Elsevier B.V.
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