Hypoxia-induced cancer-associated sugar chain facilitates tumor progression
| Project/Area Number |
17K07174
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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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| Research Field |
Tumor biology
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| Research Institution | Kumamoto University |
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Principal Investigator |
Ohtsubo Kazuaki 熊本大学, 大学院生命科学研究部(保), 教授 (30525457)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 糖鎖修飾 / がん糖鎖 / シアリルTn抗原 / 転移 / 浸潤 / 低酸素 / エクソソーム / インテグリン / 抗酸化酵素 / sTn抗原 / がん転移 |
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| Outline of Final Research Achievements |
Cancer associated carbohydrate epitopes are synthesized in the pathogenesis of cancers, however, their biological significance has been remained unclear. In the study, we revealed that Sialyl-Tn antigen up-regulates integrin protein expression without elevation of their transcription by stabilizing integrin protein on cell surface. The expression of sTn antigen in cancer cells facilitates production of exosome, which induces functional alterations in receiving cells. We obtained an inhibitor compound for the sTn antigen synthetic enzyme and found that it directly suppresses tumor invasion without any impact on cell growth. And we successfully revealed the pharmacological mechanism of the drug. It is suitable for developing next generation anti cancer drugs, which can be useful for multimodal therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
がんの進展に伴い形成されるがん微小環境はがん細胞に様々な生物学的機能を付与し、これががん治療を困難にしていることが知られている。とりわけ、低酸素環境に暴露されたがん細胞が獲得する糖鎖分子である、sTn抗原の発現はがん患者の予後の不良や転移と強く相関することが多くのがん種で報告されており、その生物学的役割を理解することは、新しいがん治療法や治療薬を開発する上で重要な意義がある。さらに、われわれはsTn抗原合成酵素の阻害剤の取得に成功しており、従前の治療法と組み合わせることで現代の多角的がん治療戦略に貢献するものと考える。
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Report
(4 results)
Research Products
(19 results)
