In HCC, the most frequent liver cancer, tumour cells resembling later stages of tumour development can bypass TGF-β-induced apoptosis and cell cycle arrest and exploit TGF-β pro-tumorigenic functions while maintaining an active canonical TGF-β signalling.22–24 Our in vitro data shows that only iCCA cells with impaired SMAD2/3/4 signalling are able to escape TGF-β suppressor effects. This evidence concerns the gene SMAD2 and hepatocellular carcinoma.