Figure 3.

Aberrant mechanisms of Hh pathway activation. (a) Type I: ligand-independent constitutive activation caused by inactivating (red star) or activating (green star) mutations in different components of the pathway. (b) Type II: autoactivation of cells by high autocrine secretion of ligands. (c) Type III: paracrine Hh activation of stromal cells dependent on tumour cell ligand secretion, which, in turn, re-stimulates the tumour via pro-oncogenic Hh target secreted factors. (d) Type IIIb: reverse paracrine activation, in which stromal cells secrete Hh ligands and activate signalling in the tumour cells. Image created with BioRender.