Transforming growth factor-β-induced plasticity causes a migratory sternness phenotype in hepatocellular carcinoma

As part of its potential pro-tumorigenic actions, Transforming Growth Factor-(TGF)-beta induces epithelial mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells. Whether EMT induces changes in tumor cell plasticity has not been fully explored yet. Here, we analyze the effects of TGF-beta on the EMT and stem-related properties of HCC cells and the potential correlation among those processes. The translational aim of the study was to propose a TGF-beta/EMT/stem gene signature that would help in recognizing HCC patients as good candidates for anti-TGF-beta therapy. Results indicate that when TGF-beta induces EMT in HCC cells, a switch in the expression of stem genes is observed and their sternness potential and migratory/invasive capacity are enhanced. However, TGF-beta may induce a partial EMT in some epithelial HCC cells, increasing the expression of mesenchymal genes and CD44, but maintaining epithelial gene expression. Epithelial cells show higher sternness potential than the mesenchymal ones, but respond to TGF-beta increasing their migratory and invasive capacity. In HCC patient samples, TGFBI expression most frequently correlates with a partial EMT, increase in mesenchymal genes and CD44 expression, as well as maintenance or over-expression of epithelial-related genes. (C) 2017 Elsevier B.V. All rights reserved.