title: The transcriptional activity of Gli1 is negatively regulated by AMPK through Hedgehog partial agonism in hepatocellular carcinoma.
abstract: The aberrant activation of the Hedgehog (Hh) signaling pathway has been implicated in a variety of malignancies, including hepatocellular carcinoma (HCC). The mammalian 5' adenosine monophosphate-activated protein kinase (AMPK) plays a crucial role in cellular energy homeostasis. However, the interaction between the Hh and AMPK signaling pathways has not been investigated to date. In the present study, to the best of our knowlege, we report for the first time the negative regulation of glioma-associated oncogene 1 (Gli1), an important downstream effector of Hh, by the AMPK signal transduction pathway. Immunoprecipitation and GST-pull down assay showed a direct interaction between AMPK and Gli1. The overexpression of AMPK induced the downregulation of Gli1 expression, while the knockdown of AMPK upregulated Gli1 expression in a relatively short period of time (24 h or less). Our data suggest that AMPK may function as an upstream molecule that regulates Gli1 expression. Therefore, AMPK may play a role in the Hh signaling pathway, through which it regulates tumorigenesis.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Qiuran
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Maode
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Qingguang
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D003514:Cyclohexylamines / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014704:Veratrum Alkaloids / Q000494:pharmacology / Q000627:therapeutic use; D000071676:Zinc Finger Protein GLI1
chemical_list: D003514:Cyclohexylamines; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D012333:RNA, Messenger; C468918:SAG compound; C509239:SHH protein, human; D013876:Thiophenes; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; D000263:Adenylate Kinase; C000541:cyclopamine