Figure 1.

Schematic representation of IGF signaling involvement in EMT. The two main signaling pathways downstream the IGF-IR are both involved in the regulation of transcription factors of the Twist, Snail, and ZEB1 families, all involved in the EMT program. The IRS-1/PI3K/Akt pathway leads to the phosphorylation and inactivation of GSK3β, thus preventing the phosphorylation and proteasome targeting of Snail and Slug. The same pathway also induces the activation of NF-kB transcription factor, which then increases the transcription of Snail and ZEB1. On the other hand, the Ras/Raf/ERK pathway is involved in the transcription of Twist and ZEB1. In turn, Snail inhibits PTEN gene transcription, thus potentiating the IRS-1/PI3K/Akt pathway. In addition, Slug increases the transcription of IGF-I, the main IGF-IR ligand.