Basal Cell Carcinoma Signaling

Basal cell carcinoma (BCC) is the most common form of skin cancer. The development of basal cell carcinoma is associated with constitutive activation of sonic hedgehog signaling.Ligand-dependent signaling by Hedgehog (Hh) homologs proceeds through association with the Patched receptor. This association relieves the Patched-mediated inhibition of the SMO receptor. Signaling via the SMO receptor releases the transcription factor Gli from an inhibitory cytoplasmic multiprotein complex. Subsequent nuclear translocation of Gli results in the expression of genes like BMP, Wnt, PTCH and Gli1 itself, resulting in cell proliferation. The mutations in SMO, PTCH1, and SHH in BCCs result in constitutive activation of target genes. Mutations in TP53, which occur at a high frequency in sporadic BCC, result in genomic instability and cell survival.