Non-canonical GLI1/2 activation by PI3K/AKT signaling in renal cell carcinoma: A novel potential therapeutic target.

•GLI1 and GLI2 are aberrantly activated in ccRCC and associated with poor survival of patients.•GLI1 and GLI2 are activated by the PI3K/AKT pathway via a SMO- and VHL-independent manner in ccRCC.•Simultaneously targeting GLIs and AKT pathways exhibits very potent efficacy to suppress tumor growth of ccRCC.