FIG. 8.

Schematic indicating how CD8-IGF-IR leads to EMT. This model is based upon studies presented in this report indicating that CD8-IGF-IR induces NF-κB, Snail, repression of E-cadherin mRNA and protein levels, and subsequently, EMT. The hierarchy is shown by the reversion of Snail mRNA levels and EMT by IGF-IR or NF-κB inhibitors. The model is supported by studies showing that IGF-IR activates Akt to repress GSK-3β, GSK-3β is a repressor of NF-κB activity and Snail mRNA and protein levels, IGF-IR activates NF-κB, and NF-κB binds the Snail promoter and increases Snail mRNA levels. PI3K, phosphatidylinositol 3-kinase.