SMAD4 and colonic neoplasm: It has been reported that TGF-beta induces VEGF expression in Smad4-null colon cancer cells [32], suggesting that TGF-beta-mediated activation of Smad4-independent pathways (i.e. MEK-Erk and p38-MAPK, etc) is involved in the up-regulation of VEGF expression, which may cooperate with other pro-oncogenic pathways to promote metastasis.