SMAD3 and hepatocellular carcinoma: TGF-β receptor I (TGF-β RI) activation has been reported to promote HCC cell invasiveness through phosphorylation of the intracellular portion of the β1 subunit of the α5β1 integrin via Smad-2 and Smad-3, leading to an inside-out conformational change and stimulating vascular invasion [66].