Abstract
Alcohol abuse synergistically heightens the development of the third most deadliest cancer hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV). Ectopically expressed TLR4 promotes liver tumorigenesis in alcohol-fed HCV Ns5a or Core transgenic mice. CD133+/CD49f + tumor-initiating stem cell-like cells (TICs) isolated from these models are tumorigenic have p53 degradation via phosphorylation of the protective protein NUMB and its dissociation from p53 by the oncoprotein TBC1D15. Nutrient deprivation reduces overexpressed TBC1D15 in TICs via autophagy-mediated degradation, suggesting a possible role of this oncoprotein in linking metabolic reprogramming and self-renewal.