Transforming growth factor beta (TGFβ) plays a key role in liver carcinogenesis. However, its action is complex, since TGFβ exhibits tumor-suppressive or oncogenic properties, depending on the tumor s Show more
Transforming growth factor beta (TGFβ) plays a key role in liver carcinogenesis. However, its action is complex, since TGFβ exhibits tumor-suppressive or oncogenic properties, depending on the tumor stage. At an early stage TGFβ exhibits cytostatic features, but at a later stage it promotes cell growth and metastasis, as a potent inducer of epithelial to mesenchymal transition (EMT). Here, we evaluated DNA methylation as a possible molecular mechanism switching TGFβ activity toward tumor progression in hepatocellular carcinoma (HCC). We report that decitabine, a demethylating agent already used in the clinic for the treatment of several cancers, greatly impairs the transcriptional response of SNU449 HCC cells to TGFβ. Importantly, decitabine was shown to induce the expression of EMT-related transcription factors (e.g., Show less