In mice bearing CRAC, the KRASG12D mutation was revealed to significantly increase the invasion and metastasis of cancer cells because conditional codeletion of Apc and Tp53 concomitant with KRASG12D mutation enabled primary and metastatic tumors to significantly upregulate the expression of the gene encoding TGF-β1, both a critical immunosuppressive cytokine [32] and a critical ligand of TGF-β/SMAD signaling that can dictate epithelial–mesenchymal transition (EMT) in CRAC cells [31]. Here, TGFB1 is linked to metastatic neoplasm.