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
{"title":"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。","authors":"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","doi":"10.1080/19490976.2023.2295384","DOIUrl":null,"url":null,"abstract":"<p><p>The anaerobic bacterium <i>Fusobacterium nucleatum</i> 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 <i>F. nucleatum</i> have only been partially uncovered. Here, we showed that <i>F. nucleatum</i> 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 <i>F. nucleatum</i> induction of this pathway increased the expression of the inflammatory cytokine IL-8 and two anti-apoptotic genes known to be implicated in CRC, <i>BIRC3</i> and <i>TNFAIP3</i>. Finally, it promoted the survival of CRC cells and reduced 5-fluorouracil chemosensitivity <i>in vitro</i>. Taken together, our results emphasize the importance of the ALPK1/TIFA pathway in <i>Fusobacterium</i> induced-CRC pathogenesis, and identify the role of ADP-H in this process.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2295384"},"PeriodicalIF":12.2000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761154/pdf/","citationCount":"0","resultStr":"{\"title\":\"<i>Fusobacterium nucleatum</i> promotes inflammatory and anti-apoptotic responses in colorectal cancer cells via ADP-heptose release and ALPK1/TIFA axis activation.\",\"authors\":\"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\",\"doi\":\"10.1080/19490976.2023.2295384\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The anaerobic bacterium <i>Fusobacterium nucleatum</i> 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 <i>F. nucleatum</i> have only been partially uncovered. Here, we showed that <i>F. nucleatum</i> 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 <i>F. nucleatum</i> induction of this pathway increased the expression of the inflammatory cytokine IL-8 and two anti-apoptotic genes known to be implicated in CRC, <i>BIRC3</i> and <i>TNFAIP3</i>. Finally, it promoted the survival of CRC cells and reduced 5-fluorouracil chemosensitivity <i>in vitro</i>. Taken together, our results emphasize the importance of the ALPK1/TIFA pathway in <i>Fusobacterium</i> induced-CRC pathogenesis, and identify the role of ADP-H in this process.</p>\",\"PeriodicalId\":12909,\"journal\":{\"name\":\"Gut Microbes\",\"volume\":\"16 1\",\"pages\":\"2295384\"},\"PeriodicalIF\":12.2000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761154/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gut Microbes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/19490976.2023.2295384\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/12/21 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gut Microbes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/19490976.2023.2295384","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/21 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Fusobacterium nucleatum promotes inflammatory and anti-apoptotic responses in colorectal cancer cells via ADP-heptose release and ALPK1/TIFA axis activation.
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.
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.
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