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

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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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Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)

This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.

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Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection

Tomoya Baba, Takeshi Ara, Miki Hasegawa … (2006)

We have systematically made a set of precisely defined, single-gene deletions of all nonessential genes in Escherichia coli K-12. Open-reading frame coding regions were replaced with a kanamycin cassette flanked by FLP recognition target sites by using a one-step method for inactivation of chromosomal genes and primers designed to create in-frame deletions upon excision of the resistance cassette. Of 4288 genes targeted, mutants were obtained for 3985. To alleviate problems encountered in high-throughput studies, two independent mutants were saved for every deleted gene. These mutants—the ‘Keio collection'—provide a new resource not only for systematic analyses of unknown gene functions and gene regulatory networks but also for genome-wide testing of mutational effects in a common strain background, E. coli K-12 BW25113. We were unable to disrupt 303 genes, including 37 of unknown function, which are candidates for essential genes. Distribution is being handled via GenoBase (http://ecoli.aist-nara.ac.jp/).

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NF-κB, inflammation, immunity and cancer: coming of age

Koji Taniguchi, Michael Karin (2018)

Fourteen years have passed since nuclear factor-κB (NF-κB) was first shown to serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. The young field of inflammation and cancer has now come of age, and inflammation has been recognized by the broad cancer research community as a hallmark and cause of cancer. Here, we discuss how the initial discovery of a role for NF-κB in linking inflammation and cancer led to an improved understanding of tumour-elicited inflammation and its effects on anticancer immunity.

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Author and article information

Journal

Journal ID (nlm-ta): Gut Microbes

Journal ID (iso-abbrev): Gut Microbes

Title: Gut Microbes

Publisher: Taylor & Francis

ISSN (Print): 1949-0976

ISSN (Electronic): 1949-0984

Publication date (Electronic, pub): 21 December 2023

Publication date (Electronic, collection): 2024

Publication date PMC-release: 21 December 2023

Volume: 16

Issue: 1

Electronic Location Identifier: 2295384

Affiliations

[a ]Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute; , Jouy-en-Josas, France

[b ]Université Paris Cité, CNRS, INSERM, Institut Cochin; , Paris, France

[c ]Université Paris-Saclay, INRAE, Metagenopolis; , Jouy-en-Josas, France

Author notes

CONTACT Nicolas Lapaque nicolas.lapaque@ 123456inrae.fr Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute; , INRAE-MICALIS UMR1319, Bat 442, Domaine de Vilvert, Jouy-en-Josas 78350, France

Present address : Nantes Université, INRAE, UMR 1280, PhAN 44,000 Nantes,France.

Author information

Camille Martin-Gallausiaux https://orcid.org/0000-0002-6193-4304

Diego Garcia-Weber https://orcid.org/0000-0001-9170-5695

Ludovica Marinelli https://orcid.org/0000-0002-2995-5105

Joël Doré https://orcid.org/0000-0002-8756-0718

Hervé M. Blottière https://orcid.org/0000-0002-8390-0607

Cécile Arrieumerlou https://orcid.org/0000-0002-6463-2897

Nicolas Lapaque https://orcid.org/0000-0003-0824-0108

Article

Publisher ID: 2295384

DOI: 10.1080/19490976.2023.2295384

PMC ID: 10761154

PubMed ID: 38126163

SO-VID: dba48f16-9cc7-43e2-a613-fe2f873be449

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

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

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Microbiology Society

Most cited references 74

Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection

NF-κB, inflammation, immunity and cancer: coming of age

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