Smoothened-independent and PI3K-dependent non-canonical GLI activation has been related to increased in vitro proliferation and clonogenicity, and in vivo tumor growth in squamous cell lung tumors (Kasiri et al., 2017), renal cell carcinoma (Zhou et al., 2016) and colon cancer (Cai et al., 2015). The gene discussed is GLI1; the disease is malignant colon neoplasm.