Using this approach, it was shown that the combination of oncogenic mutations in the Wnt (APC deletion), EGFR (KRASG12D), P53 (p53KO) and TGF-β (SMAD4KO) signaling pathways allowed the development of poorly-differentiated adenocarcinomas, endowed with metastatic potential, both at the liver and lung level [295]. This evidence concerns the gene APC and adenocarcinoma.