Development of anti-cancer drug utilizing extracellular GAPDH activity
| Project/Area Number |
18K15333
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Microbial Chemistry Research Foundation |
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Principal Investigator |
Yoshida Junjiro 公益財団法人微生物化学研究会, 微生物化学研究所, 研究員 (20712706)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | GAPDH / ケミカルバイオロジー / がんー間質相互作用 / 新規抗がん剤 / 天然物スクリーニング / がん間質相互作用 / スクリーニング / エクソソーム / 線維芽様細胞 / 共培養 / 低分子化合物 |
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| Outline of Final Research Achievements |
Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is well known as a metabolic enzyme in glycolysis, but in recent years, various localizations and functions have been reported. We have previously reported that gastric fibroblasts secrete GAPDH, and this extracellular GAPDH has the activity of suppressing the growth of cancer cells. The purpose of this research is to identify compounds that promote the secretion of GAPDH, and as a result of screening, nojirimycin-related compounds were found. In addition, from the action targets of these compounds, it was considered that the secretion pathway via the golgi apparatus is involved in the secretion of GAPDH.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題では、GAPDHの細胞外への分泌を誘導する化合物として、nojirimycin関連物質を特定した。細胞外GAPDHはがん細胞に対して増殖を抑制する活性を示すため、腫瘍内がん細胞の周辺に存在する線維芽細胞を介した新しい機序で作用する抗がん剤開発へ応用できる可能性がある。また、本研究で得たGAPDH分泌誘導活性を示す化合物はglucosidaseなどゴルジ輸送に関わるタンパクの阻害活性が報告されており、GAPDHの分泌にゴルジ輸送の関与が考えられた。GAPDHは多様な活性を有するタンパクとして近年報告されているが、細胞外GAPDHについて本研究結果により新しい制御機構が示唆された。
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Report
(5 results)
Research Products
(10 results)
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[Journal Article] Mitochondrial complex I inhibitors suppress tumor growth through concomitant acidification of the intra- and extracellular environment2021
Author(s)
J. Yoshida, T. Ohishi, H. Abe, S. Ohba, H. Inoue, I. Usami, M. Amemiya, R. Oriez, C. Sakashita, S. Dan, M. Sugawara, T. Kawaguchi, J. Ueno, Y. Asano, A. Ikeda, M. Takamatsu, G. Amori, Y. Kondoh, K. Honda, H. Osada, T. Noda, T. Watanabe, T. Shimizu, M. Shibasaki and M. Kawada
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Journal Title
iScience
Volume: 24
Issue: 12
Pages: 103497-103497
DOI
Related Report
Peer Reviewed / Open Access
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