| Project/Area Number |
17K08663
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | University of Occupational and Environmental Health, Japan (2018-2019)
Kumamoto University (2017) |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肺癌 / 癌浸潤・転移 / 癌代謝 / ANGPTL2 / GLUT3 / ZEB1 / miR-204-5p / c-Myc / IL-6 / TET2 / 癌 |
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| 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.
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| 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。
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