Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis

Takumi Mikawa; Eri Shibata; Midori Shimada; Ken Ito; Tomiko Ito; Hiroaki Kanda; Keiyo Takubo; Matilde E Lleonart; Nobuya Inagaki; Masayuki Yokode; Hiroshi Kondoh

doi:10.1016/j.isci.2020.101306

Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis

iScience. 2020 Jul 24;23(7):101306. doi: 10.1016/j.isci.2020.101306. Epub 2020 Jun 24.

Authors

Affiliations

¹ Geriatric 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.
² Joint Faculty of Veterinary Science, Yamaguchi University, Yamaguchi 753-8511, Japan.
³ Department of Pathology, Saitama Cancer Center, Saitama 362-0806, Japan.
⁴ Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
⁵ Department of Pathology, Hospital Vall de'Hebron, Barcelona 08035, Spain.
⁶ Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
⁷ Geriatric 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, Japan.
⁸ Geriatric 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. Electronic address: hkondoh@kuhp.kyoto-u.ac.jp.

Abstract

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.

Keywords: Cancer; Glycobiology; Molecular Biology.