Extracellular matrix (ECM) binding to
integrin receptors regulates cell cycle progression and survival. In adherent cells, ECM disassembly induces anoikis, the apoptotic pathway switched on by loss of adhesion. ECM-deficient
Ehlers-Danlos syndrome (EDS) fibroblasts, to adhere to rare
fibronectin (FN) fibrils, and to proliferate, only organize, as FN receptor, the
alphavbeta3 integrin. We report that in EDS cells the
alphavbeta3 integrin is bound to
talin and
vinculin, but not to
tensin, and that actin cytoskeleton is disorganized. Furthermore, in EDS cells Bcl-2 is down-regulated and
caspases are active. We provide evidence that the antibody-mediated
alphavbeta3 integrin or the FN inhibition induces anoikis in EDS cells. The
alphavbeta3 integrin transduces survival signals to pp60src-mediated
tyrosine phosphorylated
paxillin, instead than to FAK, and interacts with
EGF receptor (EGFR). This complex, when activated by
EGF and FN, signals for the rescue of EDS cells from anoikis. Therefore, EDS cells, through the
alphavbeta3 integrin-EGFR complexes, engage a
paxillin- but not FAK-mediated pathway of cell survival.