title: Human mitochondrial NAD(P)(+)-dependent malic enzyme participates in cutaneous melanoma progression and invasion.
abstract: Cutaneous melanoma is the most life-threatening neoplasm of the skin, accounting for most of the skin cancer deaths. Accumulating evidence suggests that targeting metabolism is an appealing strategy for melanoma therapy. Mitochondrial NAD(P)(+)-dependent malic enzyme (ME2), an oxidative decarboxylase, was evaluated for its biological significance in cutaneous melanoma progression. ME2 mRNA and protein expression significantly increased during melanoma progression, as evidenced by Gene Expression Omnibus analysis and immunohistochemistry on clinically annotated tissue microarrays, respectively. In addition, ME2 knockdown attenuated melanoma cell proliferation in vitro. ME2 ablation resulted in reduced cellular ATP levels and elevated cellular reactive oxygen species production, which activated the AMP-activated protein kinase pathway and inhibited acetyl-CoA carboxylase. Furthermore, ME2 expression was associated with cell migration and invasion. ME2 knockdown decreased anchorage-independent growth in vitro and tumor cell growth in vivo. These results suggested that ME2 might be an important factor in melanoma progression and a novel biomarker of invasion.
authors.affiliation: Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chang
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Gao
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan; Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chien-Ping
authors.initials: CP
authors.lastname: Chiang
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan; Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chien-Fen
authors.initials: CF
authors.lastname: Ku
authors.affiliation: Institute of Microbiology and Immunology and Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University and Hospital, Taichung, Taiwan. Electronic address: liugy@csmu.edu.tw.
authors.forename: Guang-Yaw
authors.initials: GY
authors.lastname: Liu
authors.affiliation: Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan; Institute of Genomics and Bioinformatics, National Chung-Hsing University, Taichung, Taiwan. Electronic address: hchung@dragon.nchu.edu.tw.
authors.forename: Hui-Chih
authors.initials: HC
authors.lastname: Hung
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D064593:Heterografts; D006801:Humans; D066298:In Vitro Techniques; D008291:Malate Dehydrogenase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008928:Mitochondria / Q000201:enzymology*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D008291:Malate Dehydrogenase; C495394:malic enzyme 2; human