Molecular mechanisms by which PKM1, reversing the Warburg effect, promotes tumor cell growth.
| Project/Area Number |
17K19620
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology and related fields
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| Research Institution | Miyagi Prefectural Hospital Organization Miyagi Cancer Center |
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Principal Investigator |
Tanuma Nobuhiro 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 主任研究員 (40333645)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | がん代謝 / Pkm1 / Pkm2 / Pkm / 代謝 / がん |
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| Outline of Final Research Achievements |
Expression of Pkm2, which diverts glucose-derived carbon from catabolic to biosynthetic pathways, is a hallmark of cancer. However, Pkm2 function in tumorigenesis remains controversial. We have long observed that a different Pkm isoform (Pkm1) boosts, rather than inhibits, tumor cell growth in various experimental tumor models. In this study, we found that Pkm1 activates autophagy and NAD bio-synthesis, potentially explaining how Pkm1 confer metabolic advantages to promote tumor growth cell-autonomously. As such, Pkm1 overall promotes, rather than inhibits, tumor cell proliferation. These findings strongly suggest that Pkm1 and factors related its activity are potential targets to treat small-cell lung cancer, a cancer for which few druggable mutations have been identified.
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| Academic Significance and Societal Importance of the Research Achievements |
がんにおけるPkm2/ワールブルグ効果の意義については長く論争が続いていたが、この問題に関し、重要な実験的証拠を示すことができた。これまでいくつかの細胞株を用いた実験にて、Pkm1よりも、Pkm2の方が腫瘍細胞に有利に働くとされていたが、より一般的には、むしろPkm1の方が種々の代謝メリットを腫瘍細胞にもたらすことを明らかにした。また、これまで創薬可能なゲノム変異が見つかっていない難治性肺がん（小細胞肺がん）において、Pkm1やその関連代謝経路が、新たな治療標的となる可能性を示した。
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Report
(2 results)
Research Products
(7 results)
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[Journal Article] PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth.2018
Author(s)
M Morita, T Sato, M Nomura, Y Sakamoto, Y Inoue, R Tanaka, S Ito, K Kurosawa, K Yamaguchi, Y Sugiura, H Takizaki, Y Yamashita, R Katakura, I Sato, Y Okada, H Watanabe, G Kondoh, et al.
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Journal Title
Cancer Cell
Volume: 12
Issue: 3
Pages: 355-367
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Ex vivo model of non-small cell lung cancer using mouse lung epithelial cells.2017
Author(s)
Sato T, Morita M, Tanaka R, Inoue Y, Nomura M, Sakamoto Y, Miura K, Ito S, Sato I, Tanaka N, Abe J, Takahashi S, Kawai M, Sato M, Hippo Y, Shima H, Okada Y, Tanuma N
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Journal Title
Oncol Lett.
Volume: 14(6)
Pages: 6863-6868
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Enhanced expression of PKM2 is involved in the gastric cancer development via regulating cancer specific metabolism.2017
Author(s)
Shiroki T, Yokoyama M, Tanuma N, Maejima R, Tamai K, Yamaguchi K, Oikawa T, Noguchi T, Miura K, Fujiya T, Shima H, Sato I, Kamiya N, Hatakeyama M, Iijima K, Shimosegawa T and Satoh K.
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Journal Title
Cancer Science
Volume: 印刷中
Issue: 5
Pages: 931-940
DOI
Related Report
Peer Reviewed / Open Access
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