The Hedgehog Signaling Networks in Lung Cancer: The Mechanisms and Roles in Tumor Progression and Implications for Cancer Therapy

Figure 2

HH signaling pathway during development. (a) In the absence of HH ligands, PTCH blocks ciliary localization of SMO and the GLI repressor form (mainly GLI3 repressor form [GLI3R]) suppresses induction of GLI target gene expression. (b) In the presence of HH ligands, the HH pathway is activated. Binding of HH ligand to PTCH prevents PTCH inhibition of SMO, and SMO is free to translocate into primary cilia and is fully activated. SMO then activates the GLI family, mainly GLI2. GLI2 upregulates expression of GLI1 as well as GLI target genes. GLI1 is also activated downstream of SMO. Activated GLI2 (GLI2A) and GLI1 further upregulate expression of various GLI target genes.