SMAD3 and neoplasm: It has been recently reported that hyperactive Ras mediates a decrease in TGF-β -induced Smad3 phosphorylation in the COOH-terminal and an increase in JNK-induced Smad3 phosphorylation in the linker region, shifting the TGF-β pathway from a tumor suppressive to an invasive capacity in human colorectal as well as hepatic carcinogenesis [43].