2020 Fiscal Year Final Research Report

Fusobacterium nucleatum Confers Chemoresistance by Modulating Autophagy in Esophageal Squamous Cell Carcinoma

Research Project

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Project/Area Number	18H02694
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 50020:Tumor diagnostics and therapeutics-related
Research Institution	Kumamoto University
Principal Investigator	BABA Hideo 熊本大学, 大学院生命科学研究部(医), 教授 (20240905)
Co-Investigator(Kenkyū-buntansha)	美馬浩介熊本大学, 病院, 特任助教 (00546559) 石本崇胤熊本大学, 病院, 特任准教授 (00594889) 馬場祥史熊本大学, 病院, 特任准教授 (20599708) 今村裕公益財団法人がん研究会, 有明病院消化器外科, 医長 (70583045) 原田和人熊本大学, 病院, 特任助教 (70608869)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	腸内細菌 / 食道癌 / 抗癌剤 / Fusobacterium nucleatum
Outline of Final Research Achievements	Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. The present study investigate the relationship between F. nucleatum and chemotherapeutic resistance in esophageal squamous cell carcinoma (ESCC). ESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knock down resulted in reversal of F. nucleatum-induced chemoresistance. F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy.
Free Research Field	外科腫瘍学、腫瘍免疫学、腸内細菌、エピジェネティクス
Academic Significance and Societal Importance of the Research Achievements	腸内細菌叢はプロバイオティクス（Probiotics；人体に有益な腸内細菌叢ならびにこれらを含む食品・製品）やプレバイオティクス（Prebiotics；腸内細菌叢のバランスを改善する作用がある物質）により後天的に変化させることができる。今後の研究において、消化器癌進展におけるFusobacterium nucleatumの役割がより詳細に解明されれば、がん治療の新たな創薬に繋がる可能性があると考えている。