TGF-β signaling in hepatocellular carcinoma suppression and progression

Derangements of several cell signaling pathways have been implicated in the initiation, progression, and development of hepatocellular carcinoma (HCC). One of such pathways is the activated TGF-β/Smad pathway. TGF-β inhibits proliferation and induces apoptosis in various cells types in the early tumor, and accumulation of loss-of-function mutations in the TGF-β receptor or Smad genes in tumor classify the pathway as a tumor suppressor. However, in chronic hepatitis, the cytostatic effect of TGF-β for hepatocytes attenuates as liver disease progresses from cirrhosis to HCC under persistent inflammatory microenvironments. In the later cancer period, TGF-β promotes tumor growth by modulating processes such as cell invasion, immune regulation, and microenvironment modification. Here we evaluate the suppressive and accelerant roles of TGF-β in HCC, discuss how a tumor-suppressor pathway can be so radically turned on its head and further provide some new molecular insights that may aid efforts towards targeted antitumor therapies. Moreover, we discussed the potential anti-tumor herbs through TGF-β signaling pathways.