title: E-cadherin-dependent stimulation of traction force at focal adhesions via the Src and PI3K signaling pathways.
abstract: The interplay between cadherin- and integrin-dependent signals controls cell behavior, but the precise mechanisms that regulate the strength of adhesion to the extracellular matrix remains poorly understood. We deposited cells expressing a defined repertoire of cadherins and integrins on fibronectin (FN)-coated polyacrylamide gels (FN-PAG) and on FN-coated pillars used as a micro-force sensor array (μFSA), and analyzed the functional relationship between these adhesion receptors to determine how it regulates cell traction force. We found that cadherin-mediated adhesion stimulated cell spreading on FN-PAG, and this was modulated by the substrate stiffness. We compared S180 cells with cells stably expressing different cadherins on μFSA and found that traction forces were stronger in cells expressing cadherins than in parental cells. E-cadherin-mediated contact and mechanical coupling between cells are required for this increase in cell-FN traction force, which was not observed in isolated cells, and required Src and PI3K activities. Traction forces were stronger in cells expressing type I cadherins than in cells expressing type II cadherins, which correlates with our previous observation of a higher intercellular adhesion strength developed by type I compared with type II cadherins. Our results reveal one of the mechanisms whereby molecular cross talk between cadherins and integrins upregulates traction forces at cell-FN adhesion sites, and thus provide additional insight into the molecular control of cell behavior.
authors.affiliation: Unité Mixte de Recherche 144, Centre National de la Recherche Scientifique, Institut Curie, Paris, France.
authors.forename: Audrius
authors.initials: A
authors.lastname: Jasaitis
authors.forename: Maruxa
authors.initials: M
authors.lastname: Estevez
authors.forename: Julie
authors.initials: J
authors.lastname: Heysch
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dufour
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D015820:Cadherins / Q000378:metabolism*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002645:Chickens; D016000:Cluster Analysis; D005353:Fibronectins / Q000494:pharmacology; D022001:Focal Adhesions / Q000187:drug effects / Q000201:enzymology*; D016023:Integrins / Q000378:metabolism; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000199:Actins; D015820:Cadherins; D005353:Fibronectins; D016023:Integrins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019061:src-Family Kinases