Tumor progression through epigenetics remodeling by RB-PGAM
| Project/Area Number |
17K14992
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | Kanazawa University |
|---|
Principal Investigator |
Kohno Susumu 金沢大学, がん進展制御研究所, 特任助教 (30625463)
|
|---|
| Project Period (FY) |
2017-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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|---|
| Keywords | RB / PGAM / KDM5A / エピジェネティクス |
|---|
| Outline of Final Research Achievements |
The metabolic intermediates produced in the glycolytic or TCA cycle are utilized in various pathways. We focused on the tumor suppressor gene RB, which is frequently inactivated in the malignant progression of cancer, and found that the expression of glycolytic enzyme PGAM1 is regulated by RB. In this study, we focused on the metabolic changes caused by RB inactivation and analyzed the impact given by the metabolic alteration on epigenetics. As a result, RB regulates global methylation in gastric cancer via KDM5A, and it is revealed that various glycolytic enzymes are controlled by the RB-KDM5A axis. In addition, we found that PGAM contributes RB dependent cell differentiation in myogenesis of C2C12 and adipogenesis of 3T3L1.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでに、何故がん細胞は、グルコースを積極的に利用するのか、その生理的意義と本質に迫ることができていない。本研究では、がん悪性進展課程におけるRBの不活性化に伴い、グルコースの利用が下がるという、従来の「がん特異的代謝」の概念とは逆の現象に着目し、エピジェネティクスの観点からがん代謝の理解を試みたものである。
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] Cancer stem-like properties and gefitinib resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD22019
Author(s)
Tatsunori Nishimura, Asuka Nakata, Xiaoxi Chen, Kurumi Nishi, Makiko Meguro-Horike, Soichiro Sasaki, Kenji Kita, Shin-ichi Horike, Kaori Saitoh, Keiko Kato, Kaori Igarashi, Takahiko Murayama, Susumu Kohno, Chiaki Takahashi, Naofumi Mukaida, Seiji Yano, Tomoyoshi Soga, Arinobu Tojo, Noriko Gotoh
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Journal Title
Oncogene
Volume: 38
Issue: 14
Pages: 2464-2481
DOI
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
Pages: 13872-13885
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
Pages: 1222-1236
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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