In addition to the canonical activation of GLI1 by the Hh-Ptch-Smo route, growing evidence indicates a Smo-independent stimulation of GLI1 activity in cancer, including the K-Ras, transforming growth factor-β 14, and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway 15. This evidence concerns the gene AKT1 and cancer.