title: Heat shock transcription factor 1 is a key determinant of HCC development by regulating hepatic steatosis and metabolic syndrome.
abstract: Hepatocellular carcinoma (HCC) occurrence and progression are linked tightly to progressive hepatic metabolic syndrome associated with insulin resistance, hepatic steatosis, and chronic inflammation. Heat shock transcription factor 1 (HSF1), a major transactivator of stress proteins, increases survival by protecting cells against environmental stressors. It has been implicated in the pathogenesis of cancer, but specific mechanisms by which HSF1 supports cancer development remain elusive. We propose a pathogenic mechanism whereby HSF1 activation promotes growth of premalignant cells and HCC development by stimulating lipid biosynthesis and perpetuating chronic hepatic metabolic disease induced by carcinogens. Our work shows that inactivation of HSF1 impairs cancer progression, mitigating adverse effects of carcinogens on hepatic metabolism by enhancing insulin sensitivity and sensitizing activation of AMP-activated protein kinase (AMPK), an important regulator of energy homeostasis and inhibitor of lipid synthesis. HSF1 is a potential target for the control of hepatic steatosis, hepatic insulin resistance, and HCC development.
authors: Center for Molecular Chaperone/Radiobiology and Cancer Virology, Georgia Health Sciences University, 1410 Laney Walker Boulevard, Augusta, GA 30912, USA.
authors: Xiongjie
authors: X
authors: Jin
authors: Demetrius
authors: D
authors: Moskophidis
authors: Nahid F
authors: NF
authors: Mivechi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D000076249:Heat Shock Transcription Factors; D050356:Lipid Metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D024821:Metabolic Syndrome / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D011972:Receptor, Insulin; D055372:AMP-Activated Protein Kinases