Figure 8. Proposing model for the interplay between E-cadherin, IR/IGF-IR, and bisecting GlcNAc N-glycans on the stabilization of both cell-cell adhesion and epithelial-like phenotype.

The figure summarizes our findings and shows that exogenous E-cadherin expression leads to an inhibition of IR/IGF-IR signaling, concomitantly with increased levels of bisecting GlcNAc N-glycans expression which were previously shown to stabilizes adherens-junctions, ensuring an epithelial-like phenotype [18,35]. Stimulation with insulin or IGF-I activates IR/IGF-IR signaling and downstream protein ERK 1/2, promoting a decreased expression of bisecting GlcNAc structures in general and specifically on E-cadherin which was previously shown to destabilize cell-cell adhesion [18], leading to an invasive phenotype. Concomitantly, it was observed an increased expression of the mesenchymal marker fibronectin and cytoplasmic β-catenin and E-cadherin.