title: Inhibition of the sterol regulatory element-binding protein pathway suppresses hepatocellular carcinoma by repressing inflammation in mice.
abstract: Obesity is a critical risk factor for hepatocellular carcinoma (HCC). However, it remains unknown whether inhibition of de novo lipid biosynthesis can suppress HCC. In this study, we blocked the sterol regulatory element-binding protein (SREBP) pathway, one of the key determinants of lipid homeostasis, by ablating 78-kDa cell-surface glycoprotein or SREBP cleavage-activating protein in hepatocytes, as well as by administering a chemical compound called betulin. We found that either genetically or pharmacologically inhibiting the SREBP pathway dramatically reduced diethylnitrosamine-induced HCC progression by down-regulating tumor-promoting cytokines, including interleukin (IL)-6, tumor necrosis factor alpha, and IL-1β.
  
  
  
  Inhibition of de novo lipid biosynthesis by suppressing the SREBP pathway prevents HCC. This study identifies a previously underappreciated role of the SREBP pathway in HCC and suggests a novel metabolic strategy to control liver cancer. (Hepatology 2017;65:1936-1947).
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, the Institute for Advanced Studies, Wuhan University, Wuhan, China.
authors.forename: Zhang-Sen
authors.initials: ZS
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hong-Hua
authors.initials: HH
authors.lastname: Miao
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Bo-Liang
authors.initials: BL
authors.lastname: Li
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, the Institute for Advanced Studies, Wuhan University, Wuhan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, the Institute for Advanced Studies, Wuhan University, Wuhan, China.
authors.forename: Bao-Liang
authors.initials: BL
authors.lastname: Song
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D053583:Interleukin-1beta / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental; D009765:Obesity / Q000150:complications / Q000473:pathology; D011485:Protein Binding / Q000235:genetics; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D012307:Risk Factors; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014409:Tumor Necrosis Factor-alpha