RIPK1-TRAF2 interplay on the TNF/NF-κB signaling, cell death, and cancer development in the liver

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide, with an estimated 782,000 new cases and 745,000 deaths in 2012 (1). According to the SEER Cancer Statistic Review (2), the prognosis of liver cancer patients is still poor with 5-year survival rate of 17.5%, and incidents of new cases have been rising each year at ~3% on average over the last 10 years. The prominent factors associated with HCC include chronic infection of hepatitis viruses (HVB, HVC), chronic alcohol consumption, non-alcoholic steatohepatitis, and exposure to hepatotoxins (3). Chronic liver damage following inflammation and cell death, accompanied by regenerative processes, is a feature of HCC development (3), suggesting that understanding the molecular machinery involved in cell death and regeneration in the liver may help identify molecular mechanisms of HCC.