2018 Fiscal Year Final Research Report
Elucidating the mechanism of construction of intratumor heterogeneity by tumor-associated glycan
| Project/Area Number |
16K07123
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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 | The University of Tokyo (2018)
Sapporo Medical University (2016-2017) |
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Principal Investigator |
Takamiya Rina 東京大学, 大学院医学系研究科(医学部), 特任助教 (70365419)
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 拓 札幌医科大学, 医学部, 教授 (20381254)
大坪 和明 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) |
2016-04-01 – 2019-03-31
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| Keywords | がん糖鎖 / メチル化 / メタボローム |
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| Outline of Final Research Achievements |
Sialyl-Tn antigen, which is synthesized by a glycosyltransferase ST6GalNAc-I and abnormally expressed in malignant types of cancers. To elucidate whether sialyl-Tn antigen contribute to metabolic reprogramming, we performed metabolome analysis using capillary electrophoresis mass spectrometry (CE-MS). Sialyl-Tn antigen induced pentose phosphate pathway and nucleotide synthesis in H157 cells. Sialyl-Tn antigen expressed on H157 cells also induced the production of oncometabolite, 2-hydroxyglutarate, but did not affects genome-wide alterations in DNA methylation. These findings indicate that sialyl-Tn antigen may be a key player of metabolic reprogramming in the processes of tumor progression.
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| Free Research Field |
腫瘍生化学
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| Academic Significance and Societal Importance of the Research Achievements |
これまで、がん糖鎖は腫瘍マーカーとして役割のみ捉えられていた。しかしながら、sialyl-Tn糖鎖抗原は、腫瘍マーカーとしての役割だけではなく、がん転移や酸化ストレスへの耐性への機能、さらに未だ不明な点が多いがん細胞内の代謝改変に関わる機能分子であることがわかった。このようながん細胞の代謝改変に影響を与える糖鎖はこれまで報告がなく、この研究成果の学術的意義は非常に高いと考える。
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