Establishment of novel diagnostic markers and therapy targeting lung cancer specific glycans

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17190
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Keio University
• Principal Investigator: Masuzawa Keita 慶應義塾大学, 医学部(信濃町), 共同研究員 (80772459)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 肺癌 / フコース糖鎖 / FUT3 / GDP-L-fucose / 転移

Outline of Final Research Achievements

Aberrant glycosylation is often observed as one of the hallmarks of cancer. However, the regulation of glycosylation in cancer has not been well elucidated, hampering the identification of rationale therapeutic target in cancer including lung cancer. In this study, lectin array and quantitative RT-PCR for lung cancer samples identified FUT3 as key regulator of fucosylation in lung cancer cells. Prospective induction of FUT3 in lung cancer cells promoted invasion and metastasis capacity in vitro and in vivo, respectively, partly due to fucosylation of cell surface proteins including ITGB1. Tissue microarray analysis confirmed the robust and cancer-specific expressions of FUT3 in 141 patient-derived lung cancer samples, associated with poor clinical prognosis.
These data highlight the important roles of FUT3-mediated fucosylation in lung cancer progression.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

肺癌バイオバンク検体を用いて、肺癌特異的な糖鎖及び、その制御機構・肺癌進展における機能・臨床的意義を明らかにした. FUT3を含むフコース糖鎖合成経路が肺癌に対する新規治療標的になりうることが示唆された。