DISRUPTION OF EPITHELIAL CELL-MATRIX INTERACTIONS INDUCES APOPTOSIS

Cell-matrix interactions have major effects upon phenotypic features s uch as gene regulation, cytoskeletal structure, differentiation, and a spects of cell growth control. Programmed cell death (apoptosis) is cr ucial for maintaining appropriate cell number and tissue organization. It was therefore of interest to determine whether cell-matrix interac tions affect apoptosis. The present report demonstrates that apoptosis was induced by disruption of the interactions between normal epitheli al cells and extracellular matrix. We have termed this phenomenon ''an oikis.'' Overexpression of bcl-2 protected cells against anoikis. Cell ular sensitivity to anoikis was apparently regulated: (a) anoikis did not occur in normal fibroblasts; (b) it was abrogated in epithelial ce lls by transformation with v-Ha-ras, v-src, or treatment with phorbol ester; (c) sensitivity to anoikis was conferred upon HT1080 cells or v -Ha-ras-transformed MDCK cells by reverse-transformation with adenovir us E1a; (d) anoikis in MDCK cells was alleviated by the motility facto r, scatter factor. The results suggest that the circumvention of anoik is accompanies the acquisition of anchorage independence or cell motil ity.