New potential of CCN2: Functional evaluation as a Warburg effector
| Project/Area Number |
17K19756
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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 |
Oral Science and related fields
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| Research Institution | Okayama University |
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Principal Investigator |
Kubota Satoshi 岡山大学, 医歯薬学総合研究科, 教授 (90221936)
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| Co-Investigator(Kenkyū-buntansha) |
西田 崇 岡山大学, 医歯薬学総合研究科, 准教授 (30322233)
服部 高子 岡山大学, 医歯薬学総合研究科, 助教 (00228488)
高江洲 かずみ (河田かずみ) 岡山大学, 医歯薬学総合研究科, 助教 (10457228)
滝川 正春 岡山大学, 医歯薬学総合研究科, 教授 (20112063)
青山 絵理子 岡山大学, 医歯薬学総合研究科, 助教 (10432650)
志茂 剛 北海道医療大学, 歯学部, 教授 (40362991)
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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 |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | CCN2 / CCN3 / 解糖系 / エネルギー代謝 / ワールブルグ効果 / CCN family / Warburg effect / glycolysis / carcinogenesis |
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| Outline of Final Research Achievements |
As a result of the investigation with a chondrosarcoma cell line, we found that cellular ATP level was repressed by CCN2 silencing; whereas CCN2 expression was repressed by glycolytic inhibition vice versa. These findings indicate the property of CCN2 as a Warburg booster, which is more than a Warburg effector. Furthermore, through the evaluation of the effects of glycolytic inhibition on the gene expression of all of the CCN family members, we discovered that CCN3 was contrarily induced by glycolytic inhibition. Such CCN3 induction was not observed by the inhibition of aerobic ATP synthesis by mitochondria and thus depends on glycolytic activity in the cells. Collectively, it was clarified in this study that both CCN2 and CCN3 gene expression was under a tight regulation by glycolytic activity, which eventually determines the status of energy metabolism in tumor cells.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性腫瘍の形質に強い影響力を持つCCN2とCCN3が、悪性腫瘍細胞のエネルギー代謝において果たす役割を解明した本研究は、がん細胞の新たな特質を見出し、新たながん治療の方向性を指し示すという意味で学術的にも社会的にも意義深い。
また、CCN2は組織の線維化にも深く関与するが、本研究ではCCN2の抑制がエノラーゼ阻害剤であるフッ化ナトリウムによっても起こることも確認した。これは歯磨剤に高濃度で配合されているフッ素を用いて、口腔粘膜における組織線維化を制御する手段の開発につながるという点で非常に重要である。
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Report
(3 results)
Research Products
(69 results)
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[Journal Article] Possible reparative effect of low-intensity pulsed ultrasound (LIPUS) on injured meniscus.2019
Author(s)
Kamatsuki, Y, Aoyama, E., Furimatsu, T., Miyazawa, S., Maehara, A., Yamanaka, N., Nishida, T., Kubota, S., Ozaki, T., Takigawa, M
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Journal Title
J. Cell Commun. Signal.
Volume: 13
Issue: 2
Pages: 193-207
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Physiological role of urothelial cancer-associated one long noncoding RNA in human skeletogenic cell differentiation2017
Author(s)
Ishikawa T, Nishida T, Ono M, Takarada T, Nguyen HT, Kurihara S, Furumatsu T, Murase Y, Takigawa M, Oohashi T, Kamioka H, Kubota S
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Journal Title
J Cell. Physiol.
Volume: 233(6)
Issue: 6
Pages: 4825-4840
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] FGF-1 affects the expression of MMP-13 and CCN2 in chondrocytes: possible role in osteoarthritis2018
Author(s)
El-Seoudi, A., Abd El Kader, T., Nishida T., Aoyama, E., Eguchi, T., Takigawa, M., Kubota, S.
Organizer
第31回日本軟骨代謝学会
Related Report
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[Presentation] Small compounds that turn on CCN family genes2017
Author(s)
Kubota, S., Hara, E. S., Akashi, S., Ono, M., Nishida, T., Hattori, T., Kuboki, T., Takigawa M.
Organizer
Ninth International Workshop on the CCN Family of Genes
Related Report
Int'l Joint Research
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[Presentation] CCN proteins as targets for skeletal regulation therapy2017
Author(s)
Takigawa, M., Hara, C., Kamatsuki, Y., Aoyama, E., Janune, D., Furumatsu, T., Nishida, T., Hattori, T., Yamanaka, N., Kamioka, H., Ozaki, T., Kubota, S.
Organizer
Ninth International Workshop on the CCN Family of Genes
Related Report
Int'l Joint Research
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[Presentation] Catabolic effects of FGF-1 on chondrocytes with reduced CCN2 production and its possible role in osteoarthritis.2017
Author(s)
El-Seoudi, A., Abd El Kader, T., Nishida T., Aoyama, E., Eguch, T., Takigawa, M., Kubota, S.
Organizer
Ninth International Workshop on the CCN Family of Genes
Related Report
Int'l Joint Research
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[Presentation] Catabolic effects of FGF-1 on chondrocytes with reduced CCN2 production and its possible role in osteoarthritis2017
Author(s)
El-Seoudi, A., Abd El Kader, T., Nishida T., Aoyama, E., Eguch, T., Takigawa, M., Kubota, S.
Organizer
第9回日本CCNファミリー研究会
Related Report
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[Presentation] Catabolic effects of FGF-1 on chondrocytes with reduced CCN2 production that promotes cartilage regeneration: Possible role in osteoarthritis2017
Author(s)
El-Seoudi, A., Abd El Kader, T., Nishida T., Aoyama, E., Eguch, T., Takigawa, M., Kubota, S.
Organizer
第35回日本骨代謝学会
Related Report
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