FIG. 8.

Model for integrin regulation of the cell cycle in epithelial cells. Adhesion of epithelial cells to FN is sufficient to stimulate EGFR to activate PI-3K/Akt and Erk, leading to increased synthesis of cyclin D1, subsequent activation of cdk4, and phosphorylation of a subset of sites on Rb (solid boxes). However, induction of Myc, degradation of p27, subsequent activation of cdk2, and cyclin A synthesis are poorly induced by adhesion (dashed boxes). Consequently, cells do not enter into S phase. Signals stimulated by the addition of growth factors (or by overexpression of EGFR or Myc) are required to maximally inactivate p27, stimulate cdk2 activity, and subsequently induce the synthesis of cyclin A, which is required for progression into S phase.