Elucidation of the mechanism of esophageal cancer progression via NOD/NF-kB by Fusobacterium

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08714
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: NOMOTO Daichi 熊本大学, 大学院生命科学研究部(医), 特定研究員 (70895408)
• Co-Investigator(Kenkyū-buntansha): 馬場 祥史 熊本大学, 病院, 特任准教授 (20599708) ; 岩槻 政晃 熊本大学, 大学院生命科学研究部(医), 助教 (50452777)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Fusobacterium nucleatum / Esophageal cancer / squamous cell carcinoma / NOD / NF-κB

Outline of Final Research Achievements

F. nucleatum-treated Esophagaeal squamous cell carcinoma (ESCC) cells demonstrated enhanced growth, invasion, migration ability, and NF-κB activation, as well as overexpression of NOD1 and phosphorylated (phospho-) RIPK2, compared to controls. siRNA-mediated NF-κB or NOD1 knockdown inhibited the growth of F. nucleatum. Furthermore, treated cells showed accelerated tumor growth and an increased tumor weight, with NF-κB activation in xenograft models. F. nucleatum invaded ESCC cells and induced the NF-κB pathway through the NOD1/RIPK2 pathway, leading to tumor progression.

Free Research Field

Esophageal cancer

Academic Significance and Societal Importance of the Research Achievements

Fusobacterium nucleatuｍが腫瘍進展に影響していることが分かったことから、Fusobacterium nucleatum感染を指標とした食道扁平上皮癌の新たな予後予測バイオマーカーの開発につなげたいと考えている。また、Fusobacterium nucleatumを抗菌薬、Prebiotics、Probioticsなどの薬物を通して抑制することで、Fusobacteriumu nucleatumをターゲットとした食道扁平上皮癌に対する新たな創薬シーズの開発にもつながるものと考えている。