Basal Cell Carcinoma Pathway

The development of basal cell carcinoma is associated with constitutive activation of sonic hedgehog signaling. Normally, ligand-dependent signaling by Hedgehog (Hh) homologs proceeds through binding to the Patched receptor. This binding relieves the Patched-mediated inhibition of signaling through the Smoothened (SMOH) gene product. This signaling ultimately results in the dissociation of the Gli1 transcription factor from an inhibitory complex in the cytoplasm, its subsequent translocation to the nucleus, and activation of target gene expression. The mutations in SMOH, PTCH1, and SHH in BCCs result in continuous activation of target genes. At a cellular level, sonic hedgehog signaling promotes cell proliferation. Mutations in TP53 are also found with high frequency (>50%) in sporadic BCC. (NCI Thesaurus/KEGG)

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