Hedgehog signaling pathway in cancer

Mutations in the pathway (*) or overexpression of the Hh ligand are highlighted (**) in (A) and (B) along with possible avenues of treatment using antibodies or small molecules (dashed arrows).
(A) In the absence of Hh ligand, PTCH1 inhibits surface localization of SMO and protein kinases phosphorylate Gli proteins, leading to an NH-terminal truncated form, which acts as a repressor of Hh target gene expression. GLI3 is the predominant repressor. SUFU also regulates the pathway by binding to Gli, both in the cytoplasm and in the nucleus, to prevent it from activating Hh target genes. The table lists a summary of genes implicated in cancer and potential treatment using Hh antagonists or Hh antibodies.
(B) Hh-mediated (Sonic, Indian, or Desert) inactivation of PTCH1 allows relocation of SMO to the tip of cilia, leading to downstream signaling events and the activation of the Gli proteins.