Fig 1.

Illustration of sonic hedgehog (SHH) signaling pathway. (1) SHH ligand binds to PTCH1 transmembrane protein. (2) Binding of SHH to PTCH1 relieves inhibition of smoothened (SMO). (3) Activated SMO localizes to cilium. (4) SMO releases suppressor of fused (SUFU) inhibition of GLI proteins. (5) Activated GLI proteins translocate to nucleus and activate transcription of SHH target genes (ie, GLI1, GLI2, PTCH1, and MYCN). In SHH-subgroup medulloblastoma, disruptions to SHH pathway occur through mutation of PTCH1, SMO, or SUFU and/or amplification of GLI2 or MYCN. Vismodegib inhibits SMO.