SIRT3 Enhances Glycolysis and Proliferation in SIRT3-Expressing Gastric Cancer Cells

被引:88
作者
Cui, Yang [1 ,2 ]
Qin, Lili [3 ]
Wu, Jing [1 ,2 ]
Qu, Xuan [1 ,2 ]
Hou, Chen [1 ,2 ]
Sun, Wenyan [1 ,2 ]
Li, Shiyong [4 ]
Vaughan, Andrew T. M. [3 ]
Li, Jian Jian [3 ]
Liu, Jiankang [1 ,2 ]
机构
[1] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Key Lab Biomed Informat Engn, Ctr Mitochondrial Biol & Med,Minist Educ, Xian 710049, Peoples R China
[2] Xi An Jiao Tong Univ, Frontier Inst Life Sci, Xian 710049, Peoples R China
[3] Univ Calif Davis, Dept Radiat Oncol, NCI Designated Compress Canc Ctr, Sacramento, CA 95817 USA
[4] Emory Univ, Dept Clin Pathol, Atlanta, GA 30322 USA
基金
中国国家自然科学基金;
关键词
FATTY-ACID OXIDATION; BREAST-CANCER; MITOCHONDRIAL SIRTUINS; LACTATE-DEHYDROGENASE; SUPEROXIDE-DISMUTASE; REACTIVE OXYGEN; TUMOR-GROWTH; METABOLISM; EXPRESSION; DEACETYLATES;
D O I
10.1371/journal.pone.0129834
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:17
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共 45 条
[1]   A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis [J].
Ahn, Bong-Hyun ;
Kim, Hyun-Seok ;
Song, Shiwei ;
Lee, In Hye ;
Liu, Jie ;
Vassilopoulos, Athanassios ;
Deng, Chu-Xia ;
Finkel, Toren .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (38) :14447-14452
[2]   SIRT3 and cancer: Tumor promoter or suppressor? [J].
Alhazzazi, Turki Y. ;
Kamarajan, Pachiyappan ;
Verdin, Eric ;
Kapila, Yvonne L. .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2011, 1816 (01) :80-88
[3]   Sirtuin-3 (SIRT3), a Novel Potential Therapeutic Target for Oral Cancer [J].
Alhazzazi, Turki Y. ;
Kamarajan, Pachiyappan ;
Joo, Nam ;
Huang, Jing-Yi ;
Verdin, Eric ;
D'Silva, Nisha J. ;
Kapila, Yvonne L. .
CANCER, 2011, 117 (08) :1670-1678
[4]   SIRT3 is pro-apoptotic and participates in distinct basal apoptotic pathways [J].
Allison, Simon J. ;
Milner, Jo .
CELL CYCLE, 2007, 6 (21) :2669-2677
[5]   Altered sirtuin expression is associated with node-positive breast cancer [J].
Ashraf, N. ;
Zino, S. ;
MacIntyre, A. ;
Kingsmore, D. ;
Payne, A. P. ;
George, W. D. ;
Shiels, P. G. .
BRITISH JOURNAL OF CANCER, 2006, 95 (08) :1056-1061
[6]   SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production [J].
Bell, E. L. ;
Emerling, B. M. ;
Ricoult, S. J. H. ;
Guarente, L. .
ONCOGENE, 2011, 30 (26) :2986-2996
[7]   Aerobic glycolysis by proliferating cells: A protective strategy against reactive oxygen species [J].
Brand, KA ;
Hermfisse, U .
FASEB JOURNAL, 1997, 11 (05) :388-395
[8]   Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS [J].
Chen, Yaohui ;
Zhang, Jinye ;
Lin, Yan ;
Lei, Qunying ;
Guan, Kun-Liang ;
Zhao, Shimin ;
Xiong, Yue .
EMBO REPORTS, 2011, 12 (06) :534-541
[9]   Down-regulation of miR-141 in gastric cancer and its involvement in cell growth [J].
Du, Ying ;
Xu, Yanjun ;
Ding, Ling ;
Yao, Haomi ;
Yu, Hong ;
Zhou, Tianhua ;
Si, Jianmin .
JOURNAL OF GASTROENTEROLOGY, 2009, 44 (06) :556-561
[10]   HER2-Associated Radioresistance of Breast Cancer Stem Cells Isolated from HER2-Negative Breast Cancer Cells [J].
Duru, Nadire ;
Fan, Ming ;
Candas, Demet ;
Menaa, Cheikh ;
Liu, Hsin-Chen ;
Nantajit, Danupon ;
Wen, Yunfei ;
Xiao, Kai ;
Eldridge, Angela ;
Chromy, Brett A. ;
Li, Shiyong ;
Spitz, Douglas R. ;
Lam, Kit S. ;
Wicha, Max S. ;
Li, Jian Jian .
CLINICAL CANCER RESEARCH, 2012, 18 (24) :6634-6647