Development of profiling method for cancer-specific O-GlcNAcylation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06553
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: HAGA Yoshimi 公益財団法人がん研究会, がんプレシジョン医療研究センター がんオーダーメイド医療開発プロジェクト, 研究員 (40525789)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 糖鎖 / 質量分析 / グライコプロテオミクス

Outline of Final Research Achievements

The objective of this study was to simultaneously identify cancer-specific O-GlcNAc modification sites by utilizing an original technique for comprehensive analysis of O-glycan binding sites by mass spectrometry. By establishing a method to concentrate O-glycopeptides with more than 100-fold higher enrichment efficiency, we succeeded in identifying many previously unreported O-glycosylation sites. We also analyzed colorectal cancer surgical specimens and found sites/proteins with significantly different modification frequencies in cancer tissues compared to adjacent normal areas.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

がんではタンパク質のO-GlcNAc化の昂進が高頻度に見られ、リン酸化と共にがん細胞の増殖、浸潤、転移などに関与するという報告もある。しかし、これまでO-GlcNAc修飾の変化を付加部位ごとに、高感度に、かつ網羅的に調べる技術は存在せず、O-GlcNAc修飾が持つ生理機能はごく限られた断片的な知見しか得られていない。本研究によってがん組織でO型糖鎖付加が昂進する意義やメカニズムの解明につながれば、新規糖鎖標的治療薬・診断薬のターゲット探索へも応用可能と期待される。