Regulatory mechanism of gastric differentiated type adenocarcinoma by alphaGlcNAc

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03441
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Shinshu University
• Principal Investigator: Nakayama Jun 信州大学, 学術研究院医学系, 教授 (10221459)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 糖鎖 / 胃発癌 / 炎症 / 遺伝子改変マウス / ヒト分化型胃癌

Outline of Final Research Achievements

This study investigated the involvement of IL-11 and MUC1 signalings in the regulation of pathogenesis in differentiated-type gastric adenocarcinoma by αGlcNAc. With regard to IL-11 signaling, αGlcNAc bound to the IL-11 receptor (IL-11RA) in wild-type mice and phosphorylation of STAT3 was enhanced in A4gnt KO mice compared to wild-type mice. In addition, αGlcNAc-negative and phosphorylated STAT3-positive cancer cells were observed in 8% of human differentiated-type gastric adenocarcinoma. On the other hand, analysis of A4gnt KO mice did not reveal significant findings suggesting a possible involvement of MUC1. These results combined together indicate that IL-11-mediated inhibition of STAT3 phosphorylation is one of the regulatory mechanisms of pathogenesis in gastric carcinoma.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

本研究により胃腺粘液におけるαGlcNAcの消失はIL-11シグナルの活性化を促進することで分化型胃癌の発生に結びつく可能性が示された。糖鎖による胃癌抑制機構についての知見は未だ乏しいことから、本研究成果は糖鎖病理学分野においての学術学的意義がある。またA4gnt KOマウスの胃分化型癌発生にはSTAT3の活性化が関連することが示唆され、さらにヒト胃分化型癌でも癌細胞におけるαGlcNAc陰性かつリン酸化STAT3陽性例が確認できた。この結果は、分化型胃癌の治療戦略として、IL-11/STAT3経路の阻害が有効である可能性を示している。