Anti-apoptotic signaling of the IGF-I receptor in fibroblasts following loss of matrix adhesion

The type 1 insulin-like growth factor receptor (IGF-IR) is known to protect cells from a variety of apoptotic injuries. In several instances, the anti -apoptotic effect of the wild type IGF-IR is more evident under conditions of anchorage-independence than in cells in monolayer cultures. We have inve stigated IGF-IR signaling in cells in anoikis, a form of apoptosis that occ urs when cells are denied attachment to the extra-cellular matrix. IGF-I pr otects mouse embryo fibroblasts (MEF) from anoikis caused by withdrawal of growth factors. Survival is dependent on the concentration of TGF-I and a s ufficient number of functional IGF-I receptors. In this model, IGF-I protec tion correlates best,vith ras activation and cell-to-cell aggregation, whil e PI3-kinase, Akt and MAP kinases seem to play a lesser, alternative role.