title: Glucose regulates heat shock factor 1 transcription activity via mTOR pathway in HCC cell lines.
abstract: HSF1-mediated heat shock response is activated in most tumors and plays important roles in regulating tumor homeostasis. However, the signals underlying HSF1 activation is still not completely understood. In this paper, we find that glucose, the dominant tumor energy supplement, participates in regulating HSF1's activation in HCC cell lines. The immunoblotting results indicate that the phosphorylation of HSF1/S326, a hallmark of HSF1 activation, varies between the HCC cell lines (e.g., SMMC7721, HapG2, plc/prf5, and Chang-liver). Glucose, but not 2D-glucose, can induce the phosphorylation of HSF1 at S326 and upregulate the expression of HSF1's downstream alpha B-crystallin and Hsp70 as well as the none-heat shock proteins CSK2 and RBM23 in two tested hepatocellular carcinoma cell lines (prl/prf5 and SMMC7721). Rapamycin, an inhibitor of mTOR, can suppress the glucose-induced phosphorylation of HSF1/S326 and the expression of alpha B-crystallin. Knockdown of HSF1 with shRNA enhances the glucose-depletion-mediated inhibition of plc/prf5 cell proliferation. Our data reveal that HSF1 can be activated by glucose-mTOR pathway, providing an alternative pathway for targeting HSF1 in tumor therapy.
authors.affiliation: Department of Surgery, Huai-He Hospital, Henan University, Kaifeng, Henan, China.
authors.forename: Wanli
authors.initials: W
authors.lastname: Ma
authors.affiliation: State Key Lab of Molecular Immunology and Engineering Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Medicine, Kaifeng, Henan, China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Eye Disease, Kaifeng Central Hospital, Henan University, Kaifeng, Henan, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Mu
authors.affiliation: State Key Lab of Molecular Immunology and Engineering Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Medicine, Kaifeng, Henan, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Qing
authors.affiliation: State Key Lab of Molecular Immunology and Engineering Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Medicine, Kaifeng, Henan, China.
authors.forename: Shulian
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Lab of Molecular Immunology and Engineering Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Medicine, Kaifeng, Henan, China.
authors.forename: Xiukun
authors.initials: X
authors.lastname: Cui
authors.affiliation: State Key Lab of Molecular Immunology and Engineering Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Medicine, Kaifeng, Henan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lou
authors.affiliation: State Key Lab of Molecular Immunology and Engineering Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Medicine, Kaifeng, Henan, China.
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Nephrology, The First-Affiliated Hospital of Henan University, Kaifeng, Henan, China.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Pu
authors.affiliation: State Key Lab of Molecular Immunology and Engineering Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Medicine, Kaifeng, Henan, China.
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Hu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation; D038203:alpha-Crystallin B Chain
chemical_list: C059215:CRYAB protein, human; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D034741:RNA, Small Interfering; D014157:Transcription Factors; D038203:alpha-Crystallin B Chain; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D005947:Glucose
keywords: HSF1; glucose; mTOR; phosphorylation and hepatocellular carcinoma