Molecular pathogenesis of KLRG2-mediated liver metastasis of gastric cancer cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16397
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Nagoya University
• Principal Investigator: NAKANISHI Koki 名古屋大学, 医学部附属病院, 病院助教 (10836183)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 胃癌 / 肝転移 / KLRG2 / Transcriptome解析 / コンパニオン診断

Outline of Final Research Achievements

Liver metastases of gastric cancer have an extremely poor prognosis. We performed a comprehensive analysis and identified killer cell lectin like receptor G2 (KLRG2) as a liver metastasis-specific molecule. Stable knockout of KLRG2 in gastric cancer cell lines reduced cell proliferation, migration, and cell adhesion. Forced expression of KLRG2 increased cancer cell proliferative capacity. We found that KLRG2 interfered with phosphorylation of cell cycle-related molecules. KLRG2 suppression significantly decreased tumorigenicity in mouse subcutaneous tumors. Expression analysis using 300 gastric cancer surgical specimens showed that KLRG2 expression levels in cancerous tissues were significantly correlated not only with the disease stages but also with the frequency of cumulative incidence of postoperative hematogenous metastases.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

胃癌腹膜播種においては、タキサン系薬剤の腹腔内投与を含めた新たな治療ストラテジーの開発が進んでいるものの、予後不良な肝転移においては新たな薬物療法の開発は進んでおらず、肝転移克服は重要な課題である。本研究では、次世代シーケンサーを用いた網羅的解析を肝転移に的を絞って応用することで独自性の高い標的分子KLRG2を同定し、その胃癌悪性形質形成における役割を明らかにした。この成果は、肝転移に特化した分子標的治療薬開発の糸口となる。