SMAD2 and hepatocellular carcinoma: CD44 overexpression in HCC patients and cell lines is regulated by TGF-β and confers a TGF-β–mediated mesenchymal phenotype through increased AKT/GSK-3β/β-catenin activity [42], with a further major influence on EMT-related genes, such as positive correlation with vimentin expression, negative correlation with E-cadherin expression, high percentage of phospho-Smad2–positive nuclei, and reduced disease-free and overall survival [89].