title: Loss of FBP1 facilitates aggressive features of hepatocellular carcinoma cells through the Warburg effect.
abstract: Reprogrammed metabolism has been identified as an emerging hallmark in cancer cells. It has been demonstrated that fructose-1, 6-bisphosphatase 1 (FBP1) as a rate-limiting enzyme in gluconeogenesis plays critical roles in tumor initiation and progression in several cancer types. However, function of FBP1 in hepatocellular carcinoma (HCC) is still not clear. In this study, we observed that the expression of FBP1 was obviously downregulated in the cell lines and tissues of HCC. Downregulation of FBP1 in HCC tissues was correlated with a lower overall survival rate and had a relatively higher tendency of tumor recurrence (n = 224). Silencing FBP1 could significantly promote colony formation, proliferation and metastasis of HCC cells, while ectopic overexpression of FBP1 resulted in impaired abilities of colony formation, proliferation and metastasis in vitro and in vivo. Mechanistically, silencing FBP1 facilitated glycolysis in HCC cell lines, which may be responsible for aggressiveness of HCC cells. We further found that targeting the Warburg effect using the specific inhibitor FX11 could suppress the aggressiveness of HCC cells which was mediated by loss of FBP1. These findings indicate that FBP1 appears to be a tumor suppressor in HCC. Strategies to restore the levels and activities of FBP1 might be developed to treat patients with HCC.
authors.affiliation: Basic Medical Research Centre, Medical College of Nantong University, Nantong 226021, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Cun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Basic Medical Research Centre, Medical College of Nantong University, Nantong 226021, China.
authors.forename: Fengbo
authors.initials: F
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Luo
authors.affiliation: Shanghai Medical College of Fudan University, Shanghai 200433, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Qin
authors.affiliation: The School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surry GU2 7YW, UK.
authors.forename: Einthavy
authors.initials: E
authors.lastname: Arunachalam
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Zhouhong
authors.initials: Z
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Shanghai Medical College of Fudan University, Shanghai 200433, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Wenming
authors.initials: W
authors.lastname: Cong
authors.affiliation: Basic Medical Research Centre, Medical College of Nantong University, Nantong 226021, China.|State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Qin
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004265:DNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005943:Gluconeogenesis / Q000187:drug effects / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009281:Naphthalenes / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D016601:RNA-Binding Proteins; D023041:Xenograft Model Antitumor Assays
chemical_list: C547455:3-dihydroxy-6-methyl-7-(phenylmethyl)-4-propylnaphthalene-1-carboxylic acid; D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; D009281:Naphthalenes; D016601:RNA-Binding Proteins; D004265:DNA Helicases