Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma.
Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma.
复制标题
具核梭杆菌通过调节食管鳞状细胞癌中的自噬而产生耐药性。
DOI：
10.1038/s41416-020-01198-5
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发表时间：
2021-03
影响因子：
8.8
通讯作者：
Baba H
中科院分区：
文献类型：
--
作者：
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
具核梭杆菌（Fusobacterium nucleatum, F. nucleatum）是一种涉及胃肠道肿瘤发生的肠道微生物。预测化疗反应对于开发食管癌患者的个性化治疗策略至关重要。本研究探讨了F.细胞核与食管鳞癌化疗耐药关系本文研究了F.对120例食管鳞癌切除标本和30例治疗前活检标本的细胞核和化疗反应进行了分析。使用ESCC细胞系和共培养测定的体外研究进一步揭示了化疗耐药的潜在机制。食管鳞状细胞癌伴F.细胞核感染的化疗效果较差。结果表明，F.透射电镜和激光扫描共聚焦显微镜观察ESCC细胞的细胞核。我们还观察到F. nucleatum调节内源性LC 3和ATG 7表达，以及自噬体形成，以诱导对5-FU、CDDP和多西他赛的化疗耐药。ATG 7基因敲除可使F.细胞核诱导的化学抗性。此外，免疫组化研究证实了F.检测284例食管鳞癌组织中细胞核感染和ATG 7的表达。F.细胞核通过调节自噬而赋予ESCC细胞化学抗性。这些结果表明，以F.在化疗过程中，对ESCC患者的治疗结果可能不同。
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). 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. 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. 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.
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影响因子：
6.3
作者：
Izumi, Dasiuke;Yoshida, Naoya;Baba, Hideo
通讯作者：
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影响因子：
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通讯作者：
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