title: PKM2 depletion induces the compensation of glutaminolysis through β-catenin/c-Myc pathway in tumor cells.
abstract: The metabolic activity in cancer cells primarily rely on aerobic glycolysis. Besides glycolysis, some tumor cells also exhibit excessive addition to glutamine, which constitutes an advantage for tumor growth. M2-type pyruvate kinase (PKM2) plays a pivotal role in sustaining aerobic glycolysis, pentose phosphate pathway and serine synthesis pathway. However, the participation of PKM2 in glutaminolysis is little to be known. Here we demonstrated that PKM2 depletion could provoke glutamine metabolism by enhancing the β-catenin signaling pathway and consequently promoting its downstream c-Myc-mediated glutamine metabolism in colon cancer cells. Treatment with 2-deoxy-d-glucose (2-DG), a glycolytic inhibitor, got consistent results with the above. In addition, the dimeric form of PKM2, which lacks the pyruvate kinase activities, plays a critical role in regulating β-catenin. Moreover, we found that overexpression of PKM2 negatively regulated β-catenin through miR-200a. These insights supply evidence that glutaminolysis plays a compensatory role for cell survival upon glucose metabolism impaired.
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors.forename: Haili
authors.initials: H
authors.lastname: Wu
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China; College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: lzy@sxu.edu.cn.
authors.forename: Zhuoyu
authors.initials: Z
authors.lastname: Li
mesh_terms: D000963:Antimetabolites / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003847:Deoxyglucose / Q000494:pharmacology; D005973:Glutamine / Q000235:genetics / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D000963:Antimetabolites; D002352:Carrier Proteins; D003847:Deoxyglucose; D005973:Glutamine; D008565:Membrane Proteins; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D011770:Pyruvate Kinase; D012334:RNA, Neoplasm; D013963:Thyroid Hormones; D051176:beta Catenin; D000097810:Thyroid Hormone-Binding Proteins; C533896:MIRN200 microRNA, human; C489427:MYC protein, human
keywords: Compensation; Glutaminolysis; M2-type pyruvate kinase; miR-200a; β-Catenin/c-Myc