Figure 3.

Key signalling pathways involved in EndMT modulation. (A) Graphical illustration of TGF-β signalling (B) and other common pathways in EndMT. For SMAD-dependent signalling, TGF-β binds to and activates the TGF-β I/II receptor complex. This results in the recruitment of SMAD2/3 proteins, which form a complex together with SMAD4. This is translocated into the nucleus to induce the expression of EndMT-associated genes. SMAD-independent TGF-β signalling pathways include, among others, MAPK, RHO, PI3K, and TRAF6. Other common signalling cascades that regulate EndMT include WNT, NOTCH, and FGF. Binding of WNT to the LRP5/6-FZD receptor complex mediates translocation of β-catenin into the nucleus by promoting de-assembly of the β-catenin destruction complex (APC-GSK3-Axin-CK1). NOTCH signalling activation involves the cleavage, release, and translocation of NICD into the nucleus and subsequent EndMT induction. FGF signalling involves the induction of downstream PI3K, PLCγ, and RAS signalling cascades mediated by FRS2α anchoring to FGFR and subsequent EndMT inhibition.