title: SIRT3 Enhances Glycolysis and Proliferation in SIRT3-Expressing Gastric Cancer Cells.
abstract: SIRT3 is a key NAD+-dependent protein deacetylase in the mitochondria of mammalian cells, functioning to prevent cell aging and transformation via regulation of mitochondrial metabolic homeostasis. However, SIRT3 is also found to express in some human tumors; its role in these SIRT3-expressing tumor cells needs to be elucidated. This study demonstrated that the expression of SIRT3 was elevated in a group of gastric cancer cells compared to normal gastric epithelial cells. Although SIRT3 expression levels were increased in the gastric tumor tissues compared to the adjacent non-tumor tissues, SIRT3 positive cancer cells were more frequently detected in the intestinal type gastric cancers than the diffuse type gastric cancers, indicating that SIRT3 is linked with subtypes of gastric cancer. Overexpression of SIRT3 promoted cell proliferation and enhanced ATP generation, glucose uptake, glycogen formation, MnSOD activity and lactate production, which were inhibited by SIRT3 knockdown, indicating that SIRT3 plays a role in reprogramming the bioenergetics in gastric tumor cells. Further analysis revealed that SIRT3 interacted with and deacetylated the lactate dehydrogenase A (LDHA), a key protein in regulating anaerobic glycolysis, enhancing LDHA activity. In consistence, a cluster of glycolysis-associated genes was upregulated in the SIRT3-overexpressing gastric tumor cells. Thus, in addition to the well-documented SIRT3-mediated mitochondrial homeostasis in normal cells, SIRT3 may enhance glycolysis and cell proliferation in SIRT3-expressing cancer cells.
authors.affiliation: Center for Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Radiation Oncology, NCI-designated Compressive Cancer Center, University of California Davis, Sacramento, California, 95817, United States of America.
authors.forename: Lili
authors.initials: L
authors.lastname: Qin
authors.affiliation: Center for Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Center for Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Qu
authors.affiliation: Center for Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Hou
authors.affiliation: Center for Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Clinical Pathology, Emory University, Atlanta, Georgia, 30322, United States of America.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, NCI-designated Compressive Cancer Center, University of California Davis, Sacramento, California, 95817, United States of America.
authors.forename: Andrew T M
authors.initials: AT
authors.lastname: Vaughan
authors.affiliation: Department of Radiation Oncology, NCI-designated Compressive Cancer Center, University of California Davis, Sacramento, California, 95817, United States of America.
authors.forename: Jian Jian
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Center for Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
mesh_terms: D000107:Acetylation; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004734:Energy Metabolism; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006019:Glycolysis; D006706:Homeostasis; D006801:Humans; D008819:Mice, Nude; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism; D056566:Sirtuin 3 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D056566:Sirtuin 3