Metabolic regulation by RB tumor suppressor gene
| Project/Area Number |
17H03576
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Kanazawa University |
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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 |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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| Keywords | がん / がん抑制遺伝子 / RB / 代謝 / がん代謝 / 糖代謝 / 脂質代謝 / 核酸代謝 / PGAM / がん幹細胞 |
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| Outline of Final Research Achievements |
We conducted comprehensive search of the molecular basis of RB1 function in the context of various malignant progresses, and found that SREBP transcription factors and PGAM1 and 2 are important targets of RB1. Based on these findings, we proposed a concept that RB1 regulates undifferentiated behavior of cells by controlling the metabolism in addition to regulating the cell cycle and coordinating with tissue-specific transcription factors. By analyzing in detail the mechanism by which RB1 regulates metabolism and its physiological significance, we are clarifying the true nature of cancer metabolism as a target for cancer treatment. We also obtained POCs for some of the target genes of RB1 as therapeutic targets.
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| Academic Significance and Societal Importance of the Research Achievements |
RB1は、あらゆる細胞増殖シグナルが行き着き、これを細胞周期進行制御へと結びつけるアダプタ分子であり、RB1を含むRB
パスウェイはほぼ全てのがんの制御に関わる。この分子の新規の機能を発見し、これをがん治療に活用するための標的分子を多数同定した。RB1が糖代謝、脂質代謝、核酸代謝とあらゆる代謝経路を制御する事も解明した。RB1を細胞周期と代謝をリンクする分子として位置づけた。これらの知見は、代謝面からがんを攻略する治療戦略の開発に大いに貢献すると考える。
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse.2020
Author(s)
Thumkeo, D., Katsura, Y., Nishimura, Y., Kanchanawong, P., Tohyama, K., Ishizaki, T., Kitajima, S., Takahashi, C., Hirata, T., Watanabe, N., Krummel, M. F., and Narumiya, S.
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Journal Title
Sci. Adv.
Volume: 6
Issue: 1
Pages: 2432-2432
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sphingosine-1-phosphate receptor-2 facilitates pulmonary fibrosis through potentiating IL-13 pathway in macrophages.2018
Author(s)
Zhao J, Okamoto Y, Asano Y, Ishimaru K, Aki S, Yoshioka K, Takuwa N, Wada T, Inagaki Y, Takahashi C, Nishiuchi T, Takuwa Y.
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Journal Title
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] MicroRNA-140 mediates RB tumor suppressor function to control stem cell-like activity through interleukin-6.2017
Author(s)
Yoshida A, Kitajima S, Li F, Chaoyang C, Yujiro T, Susumu K, Wan Y, Naoyuki H, Hayato M, Nishimoto Y, Nagatani N, Nishiuchi T, Thai T C, Suzuki S, Nakao S, Tanaka T, Hirose O, Barbie D A and Takahashi C.
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Journal Title
Oncotarget
Volume: 印刷中
Issue: 8
Pages: 13872-85
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Glucoraphanin ameliorates obesity and insulin resistance through adipose tissue browning and reduction of metabolic endotoxemia in mice.2017
Author(s)
Nagata N, Xu L, Kohno S, Ushida Y, Aoki Y, Umeda R, Fuke N, Zhuge F, Ni Y, Nagashimada M, Takahashi C, Suganuma H, Kaneko S and Ota T.
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Journal Title
Diabetes
Volume: 印刷中
Issue: 5
Pages: 1222-1236
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] A distinct function of the retinoblastoma protein in the control of lipid composition identified by lipidomic profiling.2018
Author(s)
Muranaka H, Hayashi A, Minami K, Kitajima S, Kohno S, Nishimoto Y, Nagatani N, Suzuki M, Kulathunga N, Sasaki N, Okada N, Matsuzaka T, Shimano H, Tada H and Takahashi C
Organizer
Abcam Cancer and Metabolism conference 2018
Related Report
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