KRAS and pancreatic ductal adenocarcinoma: Surprisingly, it is indicated that the autocrine Shh–Ptch–Smo signaling is not required in pancreatic ductal cells for the progression of pancreatic ductal adenocarcinoma (PDAC), as the deletion of SMO in the pancreas does not affect the multistage development of PDAC tumors [98]; instead, GLI1 is regulated by TGF-β and KRAS, and Gli–NF-κB oncogenic activation is required for the Kras-dependent transformation of cultured PDAC cancer cells [101].