SMO
SMO is a component of the Hedgehog signaling pathway (Figure 1). SMO and PTCH1 are transmembrane receptor proteins that deliver signals from Hedgehog ligands to cells. Mutations in PTCH1 or SMO that lead to constitutive activation of SMO are known to play a role in carcinogenesis of basal cell carcinoma, glioblastoma, medulloblastoma, and rhabdomyosarcoma (Onishi and Katano 2011).
The Hedgehog signaling pathway is a critical part of embryonic development (Athar et al. 2006). In skin, Hedgehog proteins are involved in maintenance of stem cells, development of hair follicles, development of glands, and regulation of skin growth (Athar et al. 2006).
After embryonic development, the Hedgehog pathway is not active in most human tissues (Rudin 2012). Reactivation of this pathway can lead or contribute to carcinogenesis (Onishi and Katano 2011).
SMO was identified as a therapeutic target by Hahn et al. (1996) and Johnson et al. (1996) (Rudin 2012). SMO inhibitors, exemplified by cyclopamine, bind strongly to the SMO receptor, which results in suppression of Hedgehog signaling (Robarge et al. 2009; Rudin 2012).
Figure 1. Schematic of the Hedgehog signaling pathway.