In addition to being activated by the Hh ligand/PTCH1/SMO axis, also known as the canonical Hh pathway, a growing body of evidence suggests that activation of GLI1 in some cancers is not controlled exclusively by Hh signaling but is also modulated by other pathways, such as AKT, MAPK/ERK, and KRAS pathways in an Hh ligand/PTCH1/SMO axis-independent manner, also known as noncanonical Hh signaling24. Here, SMO is linked to cancer.