RRC ID 69461
著者 Liu Y, Baba Y, Ishimoto T, Tsutsuki H, Zhang T, Nomoto D, Okadome K, Yamamura K, Harada K, Eto K, Hiyoshi Y, Iwatsuki M, Nagai Y, Iwagami S, Miyamoto Y, Yoshida N, Komohara Y, Ohmuraya M, Wang X, Ajani JA, Sawa T, Baba H.
タイトル Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma.
ジャーナル Br J Cancer
Abstract BACKGROUND:Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. Predicting the chemotherapeutic response is critical to developing personalised therapeutic strategies for oesophageal cancer patients. The present study investigated the relationship between F. nucleatum and chemotherapeutic resistance in oesophageal squamous cell carcinoma (ESCC).
METHODS:We examined the relationship between F. nucleatum and chemotherapy response in 120 ESCC resected specimens and 30 pre-treatment biopsy specimens. In vitro studies using ESCC cell lines and co-culture assays further uncovered the mechanism underlying chemotherapeutic resistance.
RESULTS: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 knockdown resulted in reversal of F. nucleatum-induced chemoresistance. In addition, immunohistochemical studies confirmed the correlation between F. nucleatum infection and ATG7 expression in 284 ESCC specimens.
CONCLUSIONS:F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy. These findings suggest that targeting F. nucleatum, during chemotherapy, could result in variable therapeutic outcomes for ESCC patients.
巻・号 124(5)
ページ 963-974
公開日 2021-3-1
DOI 10.1038/s41416-020-01198-5
PII 10.1038/s41416-020-01198-5
PMID 33299132
PMC PMC7921654
MeSH Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols / therapeutic use* Autophagy* Drug Resistance, Neoplasm* Esophageal Neoplasms / drug therapy Esophageal Neoplasms / microbiology Esophageal Neoplasms / pathology* Esophageal Squamous Cell Carcinoma / drug therapy Esophageal Squamous Cell Carcinoma / microbiology Esophageal Squamous Cell Carcinoma / pathology* Female Follow-Up Studies Fusobacterium Infections / complications* Fusobacterium Infections / microbiology Fusobacterium nucleatum / pathogenicity* Humans Middle Aged Prognosis Survival Rate
IF 5.791
リソース情報
ヒト・動物細胞 TE-8(RCB2098) TE-10(RCB2099)
一般微生物 JCM8532