Targeting metabolic reprograming during therapy-induced cellular senescence in tumor cells.
| Project/Area Number |
16K07187
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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 |
Tumor therapeutics
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| Research Institution | Miyagi Prefectural Hospital Organization Miyagi Cancer Center |
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Principal Investigator |
Sato Ikuro 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), ティッシュバンクセンター, 部長 (50225918)
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| Co-Investigator(Kenkyū-buntansha) |
田沼 延公 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) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 細胞老化 / 代謝 / Pkm1 / 抗がん剤 / Pkm2 / Pkm / 化学療法 |
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| Outline of Final Research Achievements |
Expression of Pkm2, which diverts glucose-derived carbon from catabolic to biosynthetic pathways, is selectively expressed in most of cancer cells. This prevalence of Pkm2 in cancer is thought to be associated with a phenomenon known as the Warburg effect. Chemo- and radio-therapy, inducing DNA damage, often induce cellular senescence in tumor cells (therapy-induced cellular senescence). Previously, we have found that Pkm2 expression goes down while expression of another Pkm-isoform (Pkm1) increases. In this study, we figure out how Pkm1 affect the metabolism in senescent tumor cells.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞老化に伴いグルコース取り込みが亢進することが報告されている。本研究では、取り込まれた大量のグルコースが、腫瘍細胞にてどのように代謝されるのか、重要な知見を得ることができた。他研究にて細胞老化に伴う代謝変化にPdK-Pdhの制御が関与することが示唆されていたが、加えて、Pkm1－Pkm2の制御も重要であることを明らかにできた。Pkm1がNAD合成系を活性化するという知見は、“NAD合成がSASP（senescence-associated secretory phenotype）現象と密接に関連する”とする他グループからの報告と合致しており、今後、さらなる詳細の解明が期待される。
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Report
(4 results)
Research Products
(13 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] Crucial role of carbonic anhydrase IX in tumorigenicity of xenotransplanted adult T-cell leukemia-derived cells.2017
Author(s)
Nasu K, Yamaguchi K, Takanashi T, Tamai K, Sato I, Ine S, Sasaki O, Satoh K, Tanaka N, Tanaka Y, Fukushima T, Harigae H, Sugamura K.
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Journal Title
Cancer Sci
Volume: 108
Issue: 3
Pages: 435-443
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Enhanced expression of semaphorin 3E is involved in the gastric cancer development.2016
Author(s)
Maejima R, Tamai K, Shiroki T, Yokoyama M, Shibuya R, Nakamura M, Yamaguchi K, Abue M, Oikawa T, Noguchi T, Miura K, Fujiya T, Sato I, Iijima K, Shimosegawa T, Tanaka N, Satoh K.
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Journal Title
Int J Oncol.
Volume: 49(5)
Issue: 3
Pages: 619-28
DOI
Related Report
Peer Reviewed / Open Access
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