SMAD4 and hepatocellular carcinoma: Interestingly, it has also been found in hepatoma cells that high levels of Smad4 expression are associated with poorer prognosis after surgery, and knockdown of Smad4 protein significantly inhibits colony formation and the migratory ability of hepatocytes, whereas binding of nuclear Smad4 protein to phosphorylated Smad2/3 promotes invasive metastasis in hepatoma patients.