Lysine-5 Acetylation Negatively Regulates Lactate Dehydrogenase A and Is Decreased in Pancreatic Cancer

被引：317

作者：

Zhao, Di ^{[1
,2
,3
,6
]}

Zou, Shao-Wu ^{[7
]}

Liu, Ying ^{[5
]}

Zhou, Xin ^{[1
,2
,3
,6
]}

Mo, Yan ^{[1
,2
,3
,4
]}

Wang, Ping ^{[1
,2
,6
]}

Xu, Yan-Hui ^{[1
,2
,6
]}

Dong, Bo ^{[7
]}

Xiong, Yue ^{[1
,2
,3
,6
,8
]}

Lei, Qun-Ying ^{[1
,2
,3
,4
]}

Guan, Kun-Liang ^{[1
,2
,3
,4
,9
,10
]}

机构：

[1] Fudan Univ, Shanghai Med Coll, Minist Educ, Key Lab Mol Med, Shanghai 200032, Peoples R China

[2] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200032, Peoples R China

[3] Fudan Univ, Inst Biomed Sci, Mol Cell Biol Lab, Shanghai 200032, Peoples R China

[4] Fudan Univ, Dept Biochem & Mol Biol, Shanghai 200032, Peoples R China

[5] Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Dept Pathol, Shanghai 200032, Peoples R China

[6] Fudan Univ, Sch Life Sci, Shanghai 200032, Peoples R China

[7] Tongji Univ, Shanghai Peoples Hosp 10, Dept Hepatopancreatobiliary Surg, Shanghai 200072, Peoples R China

[8] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA

[9] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92037 USA

[10] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92037 USA

来源：

CANCER CELL | 2013年 / 23卷 / 04期

关键词：

INHIBITION; GROWTH; OVEREXPRESSION; METABOLISM; ACTIVATION; EXPRESSION; PATHWAY; LIVER;

D O I：

10.1016/j.ccr.2013.02.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor cells commonly have increased glucose uptake and lactate accumulation. Lactate is produced from pyruvate by lactate dehydrogenase A (LDH-A), which is frequently overexpressed in tumor cells and is important for cell growth. Elevated transcription by c-Myc or HIF1 alpha may contribute to increased LDH-A in some cancer types. Here, we show that LDH-A is acetylated at lysine 5 (K5) and that this acetylation inhibits LDH-A activity. Furthermore, the K5-acetylated LDH-A is recognized by the HSC70 chaperone and delivered to lysosomes for degradation. Replacement of endogenous LDH-A with an acetylation mimetic mutant decreases cell proliferation and migration. Importantly, K5 acetylation of LDH-A is reduced in human pancreatic cancers. Our study reveals a mechanism of LDH-A upregulation in pancreatic cancers.

引用

页码：464 / 476

页数：13

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