title: Liver carcinogenesis: from naughty chemicals to soothing fat and the surprising role of NRF2.
abstract: The liver is a key metabolic organ that is essential for production of blood proteins, lipid and sugar metabolism and detoxification of naturally occurring and foreign harmful chemicals. To maintain its mass and many essential functions, the liver possesses remarkable regenerative capacity, but the latter also renders it highly susceptible to carcinogenesis. In fact, liver cancer often develops in the context of chronic liver injury. Currently, primary liver cancer is the second leading cause of cancer-related deaths, and as the rates of other cancers have been declining, the incidence of liver cancer continues to rise with an alarming rate. Although much remains to be accomplished in regards to liver cancer therapy, we have learned a great deal about the molecular etiology of the most common form of primary liver cancer, hepatocellular carcinoma (HCC). Much of this knowledge has been obtained from studies of mouse models, using either toxic chemicals, a combination of fatty foods and endoplasmic reticulum stress or chronic activation of specific metabolic pathways. Surprisingly, NRF2, a transcription factor that was initially thought to protect the liver from oxidative stress, was found to play a key role in promoting HCC pathogenesis.
authors.affiliation: Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, Department of Pathology and Moores Cancer Center, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA karinoffice@ucsd.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.affiliation: Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology.
authors.forename: Debanjan
authors.initials: D
authors.lastname: Dhar
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004052:Diethylnitrosamine / Q000633:toxicity; D004195:Disease Models, Animal; D006505:Hepatitis / Q000150:complications / Q000209:etiology; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D051379:Mice; D009154:Mutation; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D018384:Oxidative Stress; D020011:Protective Agents / Q000494:pharmacology
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D020011:Protective Agents; D004052:Diethylnitrosamine