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
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.
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
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
Figure 1. Schematic of the Hedgehog signaling pathway.
Suggested Citation: Rudin, C. 2015. SMO. My Cancer Genome https://www.padiracinnovation.org/content/disease/medulloblastoma/smo/?tab=0
(Updated December 4).
Last Updated: December 4, 2015
SMO in Medulloblastoma
Suggested Citation: Rudin, C. 2014. SMO in Medulloblastoma. My Cancer
(Updated August 8).
Last Updated: August 8, 2014
SMO c.1417G>C (D473H) Mutation in Medulloblastoma
The D473H mutation results in an amino acid substitution at position 473 in
SMO, from an aspartic acid (D) to a histidine (H).
a One mutation conferring
resistance to the SMO inhibitor vismodegib has been reported in the literature: D473H (Metcalfe and de Sauvage 2011;
Yauch et al. 2009).
b Due to the similarity between mechanism of action across SMO inhibitors
currently being investigated, it is believed that the D473H mutation will also confer decreased sensitivity (Rudin 2012).
Suggested Citation: Rudin, C. 2012. SMO c.1417G>C (D473H) Mutation in Medulloblastoma. My Cancer
(Updated December 3).
Last Updated: December 3, 2012
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