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2023 Fiscal Year Final Research Report

Molecular basis for determining degradation and recycling of EGFR on endosomes

Research Project

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Project/Area Number 21K07104
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionFukushima Medical University

Principal Investigator

Uemura Takefumi  福島県立医科大学, 医学部, 准教授 (80548925)

Project Period (FY) 2021-04-01 – 2024-03-31
KeywordsEGFR / メンブレントラフィック / クラスリンアダプター / エンドソーム
Outline of Final Research Achievements

Endocytic pathway of EGFR has been intensively studied. However, recycling pathway of EGFR remains poorly understood. In the present study, I found the role of clathrin adaptors AP-1 and GGA2 in EGFR recycling. They recognize EGFR on the recycling endosomes which is positive for Rab11, and knockdown of each adaptor decreases the recycling rates of EGFR. I also observed the upregulations of AP-1 and GGA2 on endosomal structures in tumors of some cancer tissues, which suggests the importance of AP-1 and GGA2 in growth and invasion of cancer cells.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

学術的意義:EGFRのリサイクリングの分子基盤はよくわかっていなかったが、本研究によりクラスリンアダプターのAP-1およびGGA2の関与を明らかにした。
社会的意義:分子標的薬によるEGFRの阻害は癌治療の戦略であるが、その使用は数年後に薬剤耐性細胞を伴う。本研究で見出したEGFR阻害は新たな癌治療戦略であり、新たな抗癌剤による癌治療の可能性が示唆された。

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Published: 2025-01-30  

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