title: Aldehyde dehydrogenase-2 (ALDH2) opposes hepatocellular carcinoma progression by regulating AMP-activated protein kinase signaling in mice.
abstract: Potential biomarkers that can be used to determine prognosis and perform targeted therapies are urgently needed to treat patients with hepatocellular carcinoma (HCC). To meet this need, we performed a screen to identify functional genes associated with hepatocellular carcinogenesis and its progression at the transcriptome and proteome levels. We identified aldehyde dedydrogenase-2 (ALDH2) as a gene of interest for further study. ALDH2 levels were significantly lower at the mRNA and protein level in tumor tissues than in normal tissues, and they were even lower in tissues that exhibited increased migratory capacity. A study of clinical associations showed that ALDH2 is correlated with survival and multiple migration-associated clinicopathological traits, including the presence of metastasis and portal vein tumor thrombus. The result of overexpressing or knocking down ALDH2 showed that this gene inhibited migration and invasion both in vivo and in vitro. We also found that ALDH2 altered the redox status of cells by regulating acetaldehyde levels and that it further activated the AMP-activated protein kinase (AMPK) signaling pathway.
  
  
  
  Decreased levels of ALDH2 may indicate a poor prognosis in HCC patients, while forcing the expression of ALDH2 in HCC cells inhibited their aggressive behavior in vitro and in mice largely by modulating the activity of the ALDH2-acetaldehyde-redox-AMPK axis. Therefore, identifying ALDH2 expression levels in HCC might be a useful strategy for classifying HCC patients and for developing potential therapeutic strategies that specifically target metastatic HCC. (Hepatology 2017;65:1628-1644).
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.|The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Hou
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.|National Center for Liver Cancer, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.|National Center for Liver Cancer, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.|National Center for Liver Cancer, Shanghai, China.
authors.forename: He-Xin
authors.initials: HX
authors.lastname: Yan
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hui-Lu
authors.initials: HL
authors.lastname: Zhang
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tang
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ying Cheng
authors.initials: YC
authors.lastname: Yang
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ximeng
authors.initials: X
authors.lastname: Lin
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Gui Juan
authors.initials: GJ
authors.lastname: Luo
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.|National Center for Liver Cancer, Shanghai, China.
authors.forename: Shanhua
authors.initials: S
authors.lastname: Tang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Oncology Business Unit, WuXi AppTec Co., Ltd., Shanghai, China.
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Gu
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ling-Hao
authors.initials: LH
authors.lastname: Zhao
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy Sciences, Shanghai, China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.|National Center for Liver Cancer, Shanghai, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhou
authors.affiliation: The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.|National Center for Liver Cancer, Shanghai, China.|State Key Laboratory for Oncogenes and Related Genes, Cancer Institute of RenJi Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000378:metabolism*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002681:China / Q000453:epidemiology; D000066630:Ectopic Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010084:Oxidation-Reduction; D011897:Random Allocation
chemical_list: C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D055372:AMP-Activated Protein Kinases