Loss of the TGF-β cytostatic response in liver cancer cells correlates with a reduced Smad3 activation

Hepatocellular carcinoma (HCC) is the third most deadliest cancer. As its phenotype is strongly heterogenic and with symptoms occurring very late, it is challenging to develop efficient therapies. TGF-ß is cytostatic towards hepatocytes in early disease, whereas it is discussed to convert to a tumor promoter during cancer progression. This potential switch in TGF-ß signaling and the heterogeneity of HCC results in a complex situation with no robust molecular mechanism established yet. We performed a very detailed analysis of TGF-ß downstream signaling in 10 HCC cell lines. Expression of TGF-ß is strongly varying…