α5β1-Integrin promotes tension-dependent mammary epithelial cell invasion by engaging the fibronectin synergy site.

ABSTRACT: Tumors are fibrotic and characterized by abundant, remodeled, and cross-linked collagen that stiffens the extracellular matrix stroma. The stiffened collagenous stroma fosters malignant transformation of the tissue by increasing tumor cell tension to promote focal adhesion formation and potentiate growth factor receptor signaling through kinase. Importantly, collagen cross-linking requires fibronectin (FN). Fibrotic tumors contain abundant FN, and tumor cells frequently up-regulate the FN receptor α5β1 integrin. Using transgenic and xenograft models and tunable two- and three-dimensional substrates, we show that FN-bound α5β1 integrin promotes tension-dependent malignant transformation through engagement of the synergy site that enhances integrin adhesion force. We determined that ligation

SUBMITTER: Miroshnikova YA 

PROVIDER: S-EPMC5662256 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature