Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis
Summary: Dysregulated glycolysis, including the cancerous Warburg effect, is closely involved in pathological mechanisms of diseased states. Among glycolytic enzymes, phosphoglycerate mutase (PGAM) has been known to exert certain physiological impact in vitro, whereas its regulatory role on glycolys...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220304934 |
| _version_ | 1818451516025995264 |
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| author | Takumi Mikawa Eri Shibata Midori Shimada Ken Ito Tomiko Ito Hiroaki Kanda Keiyo Takubo Matilde E. Lleonart Nobuya Inagaki Masayuki Yokode Hiroshi Kondoh |
| author_facet | Takumi Mikawa Eri Shibata Midori Shimada Ken Ito Tomiko Ito Hiroaki Kanda Keiyo Takubo Matilde E. Lleonart Nobuya Inagaki Masayuki Yokode Hiroshi Kondoh |
| author_sort | Takumi Mikawa |
| collection | DOAJ |
| description | Summary: Dysregulated glycolysis, including the cancerous Warburg effect, is closely involved in pathological mechanisms of diseased states. Among glycolytic enzymes, phosphoglycerate mutase (PGAM) has been known to exert certain physiological impact in vitro, whereas its regulatory role on glycolysis remains unclear. Here, we identified that PGAM plays a key role in regulating glycolysis in cancer cells but not in standard cells. Cancer-prone phenotype by PGAM overexpression in vivo was associated with upregulated glycolytic features. PGAM interacts and cooperates with Chk1 to regulate the enhanced glycolysis in cancer cells, especially under oncogenic Ras expressing conditions. Genetic or chemical interference of the PGAM-Chk1 interaction, with intact PGAM activity, abrogated the maintenance of cancerous enhanced glycolysis. Thus, the nonenzymatic function of PGAM is essential for the Warburg effect that accompanies cancerous proliferation. |
| first_indexed | 2024-12-14T21:08:26Z |
| format | Article |
| id | doaj.art-6e928af9920d45d9a207ac1e5c80a973 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-14T21:08:26Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-6e928af9920d45d9a207ac1e5c80a9732022-12-21T22:47:20ZengElsevieriScience2589-00422020-07-01237101306Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate GlycolysisTakumi Mikawa0Eri Shibata1Midori Shimada2Ken Ito3Tomiko Ito4Hiroaki Kanda5Keiyo Takubo6Matilde E. Lleonart7Nobuya Inagaki8Masayuki Yokode9Hiroshi Kondoh10Geriatric Unit, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, JapanGeriatric Unit, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, JapanJoint Faculty of Veterinary Science, Yamaguchi University, Yamaguchi 753-8511, JapanGeriatric Unit, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, JapanGeriatric Unit, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, JapanDepartment of Pathology, Saitama Cancer Center, Saitama 362-0806, JapanDepartment of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, JapanDepartment of Pathology, Hospital Vall de’Hebron, Barcelona 08035, SpainDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, JapanGeriatric Unit, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Department of Clinical Innovative Medicine, Translational Research Center, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, JapanGeriatric Unit, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; Corresponding authorSummary: Dysregulated glycolysis, including the cancerous Warburg effect, is closely involved in pathological mechanisms of diseased states. Among glycolytic enzymes, phosphoglycerate mutase (PGAM) has been known to exert certain physiological impact in vitro, whereas its regulatory role on glycolysis remains unclear. Here, we identified that PGAM plays a key role in regulating glycolysis in cancer cells but not in standard cells. Cancer-prone phenotype by PGAM overexpression in vivo was associated with upregulated glycolytic features. PGAM interacts and cooperates with Chk1 to regulate the enhanced glycolysis in cancer cells, especially under oncogenic Ras expressing conditions. Genetic or chemical interference of the PGAM-Chk1 interaction, with intact PGAM activity, abrogated the maintenance of cancerous enhanced glycolysis. Thus, the nonenzymatic function of PGAM is essential for the Warburg effect that accompanies cancerous proliferation.http://www.sciencedirect.com/science/article/pii/S2589004220304934GlycobiologyMolecular BiologyCancer |
| spellingShingle | Takumi Mikawa Eri Shibata Midori Shimada Ken Ito Tomiko Ito Hiroaki Kanda Keiyo Takubo Matilde E. Lleonart Nobuya Inagaki Masayuki Yokode Hiroshi Kondoh Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis iScience Glycobiology Molecular Biology Cancer |
| title | Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis |
| title_full | Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis |
| title_fullStr | Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis |
| title_full_unstemmed | Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis |
| title_short | Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis |
| title_sort | phosphoglycerate mutase cooperates with chk1 kinase to regulate glycolysis |
| topic | Glycobiology Molecular Biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220304934 |
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