Crosstalk between linear ubiquitin and EGFR signaling pathways in lung cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18203
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Gunma University
• Principal Investigator: Nakazawa Seshiru 群馬大学, 医学部附属病院, 助教 (60791978)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 肺癌 / 直鎖状ユビキチン / EGFR

Outline of Final Research Achievements

We focused on the linear ubiquitin (M1-Ub) and enzyme complex LUBAC. We showed the role of M1-Ub/LUBAC in lung adenocarcinoma both in vivo/in vitro. Especially, M1-Ub/LUBAC affected the EGFR signaling pathway in EGFR-mutant cell lines. LUBAC expression was associated with survival of lung adenocarcinoma patients and expression of LUBAC was elevated in adenocarcinoma cell lines. Suppression of LUBAC decreased the activation of EGFR pathway, and LUBAC inhibitor had similar effect. We conclude that LUBAC might be a treatment target for lung cancer. Also, we encountered a mutation of LUBAC components which could be involved in carcinogenesis.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

日本人の死亡原因として悪性新生物が１位で、肺癌は男女問わず高い死亡率を有する。分子標的薬など新規治療薬の開発に加え、既存の治療薬に対する耐性化の克服も重要な命題である。本研究では最も頻度が高い肺腺癌、中でもアジア人に多いEGFR変異陽性肺腺癌に着目した。そして、新規性の高いM1-Ub関連分子がEGFR変異陽性肺癌の要であるEGFRシグナル伝達経路に与える影響、及びEGFR-TKI耐性化との関連にも焦点を当てた点で学術的・社会的意義が高いと考える。