Endoplasmic Reticulum Stress and Metabolism in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for 85% to 90% of all liver cancer cases. It is a hepatocyte-derived primary tumor, causing 550,000 deaths per year, ranking it as one of the most common cancers worldwide. The liver is a highly metabolic organ with multiple functions, including digestion, detoxification, breakdown of fats, and production of bile and cholesterol, in addition to storage of vitamins, glycogen, and minerals, and synthesizing plasma proteins and clotting factors. Due to these fundamental and diverse functions, the malignant transformation of hepatic cells can have a severe impact on the liver's metabolism. Furthermore, tumorigenesis is often accompanied by activation of the endoplasmic reticulum (ER) stress pathways, which are known to be highly intertwined with several metabolic pathways. Because HCC is characterized by changes in the metabolome and by an aberrant activation of the ER stress pathways, the aim of this review was to summarize the current knowledge that links ER stress and metabolism in HCC, thereby focusing on potential therapeutic targets.