The activation of GLI genes can occur through canonical or noncanonical mechanisms, with the RAS-RAF-MEK-ERK pathway (Figure 5) being the most frequently involved in noncanonical mechanisms and responsible for the proliferation of colon cancers, as is the PI3K-AKT-mTOR pathway in pancreatic cancer [147,148,149]. Here, GLI1 is linked to malignant colon neoplasm.