PMC

Hh signaling pathway. In the absence of Hh ligand, Ptch exerts an inhibitory effect on Smo, and no downstream signaling occurs. In the presence of Hh ligand binding to Ptch, the suppression of Smo is released. Smo interacts with Suppressor of fused (SUFU), which promotes the activation and nuclear translocation of Gli1. Gli1 translocation results in the transcription of Hh target genes.
Abbreviations: Hh, Hedgehog; Ptch, Patched; Smo, Smoothened, COS, Ccoastal-2; FU, Fused.

Modes of Hh pathway signaling. (A) Type I Hh signaling is activated by specific mutations within pathway genes within tumor cells, resulting in ligand-independent constitutive activation. (B) Type II Hh signaling results from autocrine signaling from tumor cell to tumor cell. (C) Type IIIa activation results from secretion of Hh ligand by tumor cells, resulting in pathway activation in surrounding tumor stroma. (D) Type IIIb Hh signaling results from Hh ligand secretion by tumor stroma, resulting in activation of the pathway within tumor cells themselves.
Abbreviation: Hh, Hedgehog.