Mechanisms of cancer metabolism and drug resistance regulated by S1P in triple negative breast cancer
| Project/Area Number |
18K19576
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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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| Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
若井 俊文 新潟大学, 医歯学系, 教授 (50372470)
五十嵐 道弘 新潟大学, 医歯学系, 教授 (50193173)
崎村 建司 新潟大学, 脳研究所, フェロー (40162325)
阿部 学 新潟大学, 脳研究所, 准教授 (10334674)
奥田 修二郎 新潟大学, 医歯学系, 准教授 (00512310)
土田 純子 新潟大学, 医歯学総合病院, 専任助教 (90769415)
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| Project Period (FY) |
2018-06-29 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 脂質メディエーター / スフィンゴシン－1－リン酸 / 乳癌 / スフィンゴシン-1-リン酸 / スフィンゴシンキナーゼ1型 / 癌代謝 / 治療 / トリプルネガティブ乳癌 / 薬剤耐性 |
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| Outline of Final Research Achievements |
The sphingosine-1-phosphate (S1P)-producing enzyme SphK1 was knockout (KO) on the triple negative breast cancer (TNBC) cell line, and it was confirmed that SphK1 contributed to cell proliferation, migration, and infiltration. Lipidomics analysis of surgical specimens of breast cancer showed that TNBC showed significantly higher S1P concentrations in tissues and serum than other subtypes, suggesting that S1P plays an important role. Metabolome analysis significantly reduced glycolytic and TCA cycle metabolites in SphK1KO cells, as well as reduced glutathione production associated with oxidative stress and drug resistance, suggesting that S1P may be involved in these pathways.
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| Academic Significance and Societal Importance of the Research Achievements |
近年のがん研究の飛躍的な進歩にも関わらず、TNBCをはじめとする一部の癌では、遺伝子変異に乏しく、タンパク分析を行っても治療に直接結びつくような異常が見つかりにくい。本研究は、脂質であることから研究することが難しく、これまで看過されてきた脂質メディエーターを介した癌代謝制御機構に着目し、TNBCの高悪性度の病態メカニズムの追究を行った。本研究において、TNBCの薬剤耐性における脂質メディエーターを介した癌代謝制御機構の役割を解明することによって、S1Pを標的とした新規治療開発の足掛かりとなる可能性がある。
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Report
(4 results)
Research Products
(12 results)
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[Presentation] Sphingosine-1-phospate Signaling Regulates Drug Resistance Mediated by Glutathione2019
Author(s)
Nagahashi M, Tsuchida J, Moro K, Ikarashi M, Nakajima M, Abe M, Saito T, Komatsu M, Soga T, Takabe K, Sakimura K, Wakai T
Organizer
The 14th Annual Academic Surgical Congress
Related Report
Int'l Joint Research
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[Presentation] Tumor mutation burden in triple negative breast cancer patients in Japan2018
Author(s)
Nagahashi M, Ling Y, Hayashida T, Kitagawa Y, Futamura M, Yoshida K, Kuwayama T, Nakamura S, Toshikawa C, Yamauchi H, Yamauchi T, Kaneko K, Kanbayashi C, Sato N, Miyoshi Y, Tsuchida J, Nakajima M, Shimada Y, Ichikawa H, Lyle S, Takabe K, Okuda S, Wakai T
Organizer
2018 American Society of Clinical Oncology Annual Meeting
Related Report
Int'l Joint Research
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