title: PKM2 Thr454 phosphorylation increases its nuclear translocation and promotes xenograft tumor growth in A549 human lung cancer cells.
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.
authors.affiliation: Center for Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, China. Electronic address: tomsyu@163.com.
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Liangqian
authors.initials: L
authors.lastname: Huang
authors.affiliation: Center for Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, China.
authors.forename: Pengyun
authors.initials: P
authors.lastname: Qiao
authors.affiliation: Center for Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, China.
authors.forename: Aifang
authors.initials: A
authors.lastname: Jiang
authors.affiliation: Center for Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Plastic Surgery Institute of Weifang Medical University, Weifang, Shandong, 261041, China.
authors.forename: Shengjian
authors.initials: S
authors.lastname: Tang
authors.affiliation: Plastic Surgery Institute of Weifang Medical University, Weifang, Shandong, 261041, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Center for Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, China. Electronic address: ren@wfmc.edu.cn.
authors.forename: Chune
authors.initials: C
authors.lastname: Ren
mesh_terms: D000072283:A549 Cells; D021581:Active Transport, Cell Nucleus; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism; D010427:Pentose Phosphate Pathway; D010766:Phosphorylation; D011770:Pyruvate Kinase / Q000737:chemistry / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism; D013963:Thyroid Hormones / Q000737:chemistry / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D011770:Pyruvate Kinase; D013912:Threonine; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins
keywords: Cancer; Glycolysis; Phosphorylation; Pyruvate kinase M2; Xenograft