Primary Focus

The focus of our research is centered on deciphering the molecular and cellular mechanisms driving development of hepatocellular carcinoma (HCC). Liver cancer has been escalated to be the 2nd cause of cancer-related death worldwide. Many of the classical onocgenic pathways have been shown to play critical roles in human liver tumorigenesis, and therefore become drug targets in therapy. Unfortunately, these mechanism-based approaches have achieved very little or at most temporary effect in the clinical treatment. Consistent to this disappointing outcome in therapeutics, we and others have uncovered anti-oncogenic roles for many pro-oncogenic molecules in the liver. We believe that these apparently “conflicting” data do not necessarily obscure the mechanisms underlying hepatocarcinogenesis. In contrast, elucidating the “paradoxical” roles of these molecules will lead to a paradigm shift in liver cancer, and may provide novel diagnostic and therapeutic strategies for this malignant disease.

Deciphering the Pro- and Anti-Oncogenic Activities of Molecules in Hepatocarcinogenesis (Feng, Cancer Cell 21, 150, 2012). 

(A) MET, NF-kB, Stat3, Jnk, Shp2, and b-catenin constitute pathways that normally promote cell survival and proliferation. Aberrant activation or overexpression of these molecules enhances cell transformation and tumorigenesis. (B) Removal or inactivation of these protumorigenic molecules, which normally causes hepatocyte damage and death, also enhances HCC development under certain conditions. (C) One hypothesis is that loss of a prosurvival signal enhances chronic hepatic damage, increases production of inflammatory cytokines, and triggers excessive compensatory proliferation of hepatocytes and/or progenitor cells, resulting in elevated hepatocarcinogenesis.