Fig. 10: Ras/MAPK and PI3K/AKT co-recruitment is necessary for tumour extrusion.

Initiation by a oncogenic hit (red) allows ERK activation in rare epithelial cells. This induces production of two growth factors in these cells, EGF/Spitz and IGF-Ilp6 (violet). EGF/Spitz re-activates ERK in an autocrine manner, via EGFR activation (amplification loop, blue). This sustains an increase in the growth factors production. Subsequently, EGFR/InR autocrine activation induces a coordinated recruitment of the Ras/MAPK and PI3K/AKT/TOR pathways. This finally allows formation of invasive tumours outside the epithelial compartment.