Figure 3

Regulation of cell adhesion by RAS/MAPK, RAS/PI3K/AKT and β-catenin signalling. In lung NSCLC, constitutive signalling is caused by mutational activation of components of the RAS/MAPK and/or RAS/PI3K/AKT pathways that endows tumour cells with enhanced proliferation and survival in the absence of a growth factor (GF). Loss of E-cadherin expression and disruption of a functional E-cadherin complex at the adherens junction are two events that occur in human lung cancers. Inducible disruption of the functional E-cadherin complex in a RAF oncogene-driven NSCLC mouse model led to the loss of adherens junction function and deadhesion of neighbouring tumour cells. In addition, nuclear β-catenin activity was instrumental for increased proliferation and survival of tumour cells, as well as the induction of angiogenic factors that facilitated the growth of a tumour vasculature (angiogenic switch) and changes in cell fate integrity (dysplasia).