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Biochem Biophys Res Commun. 2016 May 13;473(4):953-958. doi: 10.1016/j.bbrc.2016.03.160. Epub 2016 Apr 1.

PKM2 Thr454 phosphorylation increases its nuclear translocation and promotes xenograft tumor growth in A549 human lung cancer cells.

Author information

1
Center for Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, China. Electronic address: tomsyu@163.com.
2
Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, 200025, China.
3
Center for Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, China.
4
Plastic Surgery Institute of Weifang Medical University, Weifang, Shandong, 261041, China.
5
Center for Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, China. Electronic address: ren@wfmc.edu.cn.

Abstract

Pyruvate kinase M2 (PKM2) is a key enzyme of glycolysis which is highly expressed in many tumor cells, and plays an important role in the Warburg effect. In previous study, we found PIM2 phosphorylates PKM2 at Thr454 residue (Yu, etl 2013). However, the functions of PKM2 Thr454 modification in cancer cells still remain unclear. Here we find PKM2 translocates into the nucleus after Thr454 phosphorylation. Replacement of wild type PKM2 with a mutant (T454A) enhances mitochondrial respiration, decreases pentose phosphate pathway, and enhances chemosensitivity in A549 cells. In addition, the mutant (T454A) PKM2 reduces xenograft tumor growth in nude mice. These findings demonstrate that PKM2 T454 phosphorylation is a potential therapeutic target in lung cancer.

KEYWORDS:

Cancer; Glycolysis; Phosphorylation; Pyruvate kinase M2; Xenograft

PMID:
27045080
DOI:
10.1016/j.bbrc.2016.03.160
[Indexed for MEDLINE]

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