Fusobacterium nucleatum promotes inflammatory and anti-apoptotic responses in colorectal cancer cells via ADP-heptose release and ALPK1/TIFA axis activation.

IF 12.2 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut Microbes Pub Date : 2024-01-01 Epub Date: 2023-12-21 DOI:10.1080/19490976.2023.2295384

Camille Martin-Gallausiaux, Laurène Salesse, Diego Garcia-Weber, Ludovica Marinelli, Fabienne Beguet-Crespel, Vincent Brochard, Camille Le Gléau, Alexandre Jamet, Joël Doré, Hervé M Blottière, Cécile Arrieumerlou, Nicolas Lapaque

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引用次数: 0

Abstract

The anaerobic bacterium Fusobacterium nucleatum is significantly associated with human colorectal cancer (CRC) and is considered a significant contributor to the disease. The mechanisms underlying the promotion of intestinal tumor formation by F. nucleatum have only been partially uncovered. Here, we showed that F. nucleatum releases a metabolite into the microenvironment that strongly activates NF-κB in intestinal epithelial cells via the ALPK1/TIFA/TRAF6 pathway. Furthermore, we showed that the released molecule had the biological characteristics of ADP-heptose. We observed that F. nucleatum induction of this pathway increased the expression of the inflammatory cytokine IL-8 and two anti-apoptotic genes known to be implicated in CRC, BIRC3 and TNFAIP3. Finally, it promoted the survival of CRC cells and reduced 5-fluorouracil chemosensitivity in vitro. Taken together, our results emphasize the importance of the ALPK1/TIFA pathway in Fusobacterium induced-CRC pathogenesis, and identify the role of ADP-H in this process.

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核酸镰刀菌通过 ADP-庚糖释放和 ALPK1/TIFA 轴激活促进结直肠癌细胞的炎症和抗凋亡反应。

厌氧菌核酸镰刀菌与人类结直肠癌（CRC）密切相关，被认为是导致该疾病的重要因素。目前仅部分揭示了核酸桿菌促进肠道肿瘤形成的机制。在这里，我们发现 F. nucleatum 会向微环境释放一种代谢物，这种代谢物会通过 ALPK1/TIFA/TRAF6 途径强烈激活肠上皮细胞中的 NF-κB。此外，我们还发现释放的分子具有 ADP-庚糖的生物学特性。我们观察到，F. nucleatum 诱导的这一途径增加了炎性细胞因子 IL-8 和两个已知与 CRC 有关的抗凋亡基因 BIRC3 和 TNFAIP3 的表达。最后，它还促进了 CRC 细胞的存活，降低了体外 5 氟尿嘧啶化疗的敏感性。综上所述，我们的研究结果强调了ALPK1/TIFA通路在镰刀菌诱导的CRC发病机制中的重要性，并确定了ADP-H在这一过程中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gut Microbes Medicine-Microbiology (medical)

CiteScore

18.20

自引率

3.30%

发文量

196

审稿时长

10 weeks

期刊介绍： The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more. Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.