Correlations between the Sonic Hedgehog pathway and basal cell carcinoma.
The Hedgehog (HH) family of intercellular signaling proteins has some essential functions in patterning both invertebrate and vertebrate embryos. Identified as an important regulator of segment polarity and tissue organization in flies, the HH pathway can also play a significant role in human development and in cutaneous carcinogenesis. The family received their name because when the D. melanogaster HH protein malfunctions the mutant fly ends up looking like a small prickly ball, similar to a curled up hedgehog. The Sonic hedgehog (SHH) pathway is implicated in the etiology of the most common human cancer, the basal cell carcinoma (BCC). Mutations in the receptor of SHH, the patched gene (PTCH), have been characterized in sporadic BCCs as well as those from patients with the rare genetic syndrome nevoid BCC. Human PTCH is mutated in sporadic as well as hereditary BCCs, and inactivation of this gene is probably a necessary if not sufficient step for tumorigenesis. Delineation of the biochemical pathway in which PTCH functions may lead to rational medical therapy for skin cancer and possibly other tumors.
Lupi
Omar
O
Universidade Federal do Rio de Janeiro (UFRJ) and Instituto de Dermatologia Prof Rubem Azulay/Santa Casa RJ, Rio de Janeiro, Brazil. omarlupi@globo.com
D000818:Animals; D002280:Basal Cell Carcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000072086:Smoothened Receptor; D014704:Veratrum Alkaloids / Q000494:pharmacology
D051858:Forkhead Transcription Factors; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014704:Veratrum Alkaloids; C000541:cyclopamine