The research for developing a method for controlling cancer invasion and metastasis by elucidating the mechanism of cancer metabolic change

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08663
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: University of Occupational and Environmental Health, Japan (2018-2019); Kumamoto University (2017)
• Principal Investigator: Endo Motoyoshi 産業医科大学, 医学部, 教授 (40398243)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 肺癌 / 癌浸潤・転移 / 癌代謝 / ANGPTL2

Outline of Final Research Achievements

It is known that the change of energy metabolism from oxidative phosphorylation to glycolysis in cancer cells promotes tumor aggressiveness and malignancy. In this study, we showed that tumor cell-derived ANGPTL2 upregulated expression of GLUT3 and activated glycolytic metabolism. ANGPTL2 signaling through integrin α5β1 increased GLUT3 expression through increasing TGF-β signaling and its downstream transcription factor ZEB1. ANGPTL2 knockdown in lung cancer cell lines decreased TGF-β, ZEB1 and GLUT3 expression and antagonized glycolytic metabolism. In addition, ANGPTL2 expression levels correlated with GLUT3 expression in primary tumor cells from lung cancer patients. Overall, tumor cell-derived ANGPTL2 expression promotes activities associated with glycolytic metabolism in lung cancer cells by activating TGF-β-ZEB1-GLUT3 signaling.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

慢性炎症は様々な疾患の増悪因子であり、癌においても浸潤能や転移能を高めることが知られている。本研究では、慢性炎症因子の1つであるANGPTL2が肺癌細胞に作用すると、癌細胞の代謝が変化し癌細胞の悪性度（転移能や浸潤能の亢進）が高まることを明らかにした。肺癌患者のサンプルを用いた解析においても、in vitro実験の結果と同様の結果を得られていることから、肺癌細胞のANGPTL2発現抑制は癌浸潤・転移抑制につながることが示された。