Elucidation and application of early brain metastasis mechanism by Warburg regulator MPC
| Project/Area Number |
18K08704
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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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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Osaka International Cancer Institute |
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Principal Investigator |
KUDO Toshihiro 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 腫瘍内科副部長 (20593859)
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 太郎 大阪大学, 医学系研究科, 寄附講座教授 (40368303)
小関 準 大阪大学, 医学系研究科, 特任助教(常勤) (20616669)
坂井 大介 大阪大学, 医学部附属病院, 特任講師(常勤) (10621071)
石井 秀始 大阪大学, 医学系研究科, 特任教授(常勤) (10280736)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 化学療法 / 癌 / シングル細胞 / がん / 転移 / 代謝 / ピルビン酸キナーゼ / 創薬 / バイオマーカー |
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| Outline of Final Research Achievements |
Brain metastases show strong treatment resistance, and the current situation is that current anticancer drugs, molecular-targeted therapies, and radiation therapy do not provide fundamental efficacy. Therefore, it is essential to elucidate the treatment resistance rooted in the true nature of cancer and to develop a treatment method. According to our research results, the regulation of anaerobic glycolysis by the key molecule MPC (mitochondrial pyruvate transporter) of the Warburg effect induces epithelial-mesenchymal transformation (EMT) to make cancer stem cells, and multiple It was revealed that the treatment resistance to the anticancer drug was acquired. For cancer cells that are relatively prone to brain metastasis as a mechanism, the role of MPC in early brain metastasis is investigated by single cells from the three-dimensional reconstruction of the cell group that constitutes the blood-brain barrier (BBB) toward the future clinical application.
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| Academic Significance and Societal Importance of the Research Achievements |
より精密な診断のためのバイオマーカーの探索や、新たな治療標的を提示することができるようになり、がん代謝を介したMPCと細胞の形質転換の関連性を通じて、創薬の標的化、機序の解明、抵抗性の予測を通じて、難治がんの精密医療に貢献することができた。手術切除試料を用いた動物モデル(PDX: patient derived xenograft)と、三次元組織構築を構成する細胞群の解析から、早期の転移浸潤における責任分子の役割を究明し、創薬の標的化、機序の解明、抵抗性の予測を通じて、難治がんの精密医療に貢献することができた。
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Distinct methylation levels of mature microRNAs in gastrointestinal cancers2019
Author(s)
Konno Masamitsu、Koseki Jun、Asai Ayumu、Yamagata Akira、Shimamura Teppei、Motooka Daisuke、Okuzaki Daisuke、Kawamoto Koichi、Mizushima Tsunekazu、Eguchi Hidetoshi、Takiguchi Shuji、Satoh Taroh、Mimori Koshi、Ochiya Takahiro、Doki Yuichiro、Ofusa Ken、Mori Masaki、Ishii Hideshi
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Journal Title
Nature Communications
Volume: 10
Issue: 1
Pages: 3888-3888
DOI
Related Report
Peer Reviewed / Open Access
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