INSULIN-LIKE GROWTH FACTOR-I-MEDIATED SURVIVAL FROM ANOIKIS - ROLE OFCELL-AGGREGATION AND FOCAL ADHESION KINASE

Anoikis is a form of cell death that occurs when cells are denied atta chment to the extra-cellular matrix. Using p6 cells, that are 3T3 cell s overexpressing the type 1 insulin-like growth factor receptor (IGF-I R), we show that these cells undergo apoptosis when seeded on polyHEMA plates in serum-free medium (SFM). IGF-I protects p6 cells from anoik is, without inducing mitogenesis or DNA synthesis. in the surviving p6 cells in suspension cultures, the focal adhesion kinase (FAK) is tyro syl phosphorylated by IGF-1, although this phosphorylation occurs only after several hours. The importance of FAK in protection from anoikis is confirmed by v-src-transformed R-cells, in which FAK is constituti vely phosphorylated, that survive even in SFM. Surviving cells, whethe r p6 or v-src transformed, tend to form large cell aggregates, whose a ppearance precedes the phosphorylation of FAK. These and other finding s suggest that FAK phosphorylation in the case of IGF-I is a mediated effect rather than a direct one. When p6 cells are plated on polyHEMA dishes, ICF-I induces cell aggregation and this aggregation correlates with survival and the eventual phosphorylation of FAK. J. Cell. Physi ol. 176:648-657, 1998. (C) 1998 Wiley-Liss, Inc.