期刊
CANCER CELL
卷 23, 期 4, 页码 464-476出版社
CELL PRESS
DOI: 10.1016/j.ccr.2013.02.005
关键词
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资金
- Chinese Ministry of Sciences and Technology 973 [2009CB918401, 2011CB910600, NCET-09-0315]
- NSFC [31271454, 81225016]
- NSFC-NIH [81110313]
- 100 Talents Program of Shanghai Health, the Scholar of Dawn Program of Shanghai Education Commission, Shanghai Outstanding Academic Leader
- Shanghai Key basic research program [12JC1401100]
- NIH
- Fudan University Medical School Graduate Student Ming Dao Project funds
- Chinese Ministry of Education 985 Program
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.
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