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Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy
Open accessAbstract
Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum orchestrates a molecular network of the Toll-like receptor, microRNAs, and autophagy to clinically, biologically, and mechanistically control colorectal cancer chemoresistance. Measuring and targeting F. nucleatum and its associated pathway will yield valuable insight into clinical management and may ameliorate colorectal cancer patient outcomes.
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“a higher abundance of F nucleatum (present in approximately 10%–15% of tumors) has been associated with advanced disease stage, higher risk of recurrence, and shorter patient survival times.23, 26, 28”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [28]
In the citing paper
“Bioinformatic and functional studies indicated that F nucleatum activates innate immune responses, via TLR4 and MYD88, resulting in loss of specific microRNAs. This resulted in activation of autophagy activation and promotion of chemoresistance in patients with CRC.28”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [28]
In the citing paper
“F nucleatum was promotes resistance of CRC cells to chemotherapy.28”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [28]
In the citing paper
“Patients with post-chemotherapy recurrence had a higher abundance of F nucleatum in tumor tissues.28, 193”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [28]
In the citing paper
“(iii) chemoresistance via direct microbial metabolism (cytidine deaminase degradation of gemcitabine) in pancreatic cancer or indirect amplification of cancer cell autophagy in colorectal cancer (14, 104)”
From The microbiome and human cancer (2021) · cites this paper as [104]
In the citing paper
“regulate chemoresistance via direct drug metabolism by microbes [415, 416]”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [416]
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Metadata
- Authors
- Yu, T., Guo, F., Yu, Y., Sun, T., Ma, D., Han, J., Qian, Y., Kryczek, I., Sun, D., Nagarsheth, N., Chen, Y., Chen, H., Hong, J., Zou, W., & Fang, J.-Y.
- Affiliations
- Shanghai Jiao Tong University (CN)
- University of Michigan (US)
- Corresponding author
- Chen, Yingxuan
- Chen, Haoyan
- Hong, Jie
- Zou, Weiping
- Fang, Jing-Yuan
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 170
- Issue
- 3
- Pages
- 548-563.e16
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5767127
- OpenAlex
- W2742147437
- Cited by
- 2,198
- References
- 50
- Citations by year
- 2026: 265 · 2025: 291 · 2024: 300 · 2023: 323 · 2022: 287 · 2021: 268 · 2020: 214 · 2019: 124 · 2018: 105 · 2017: 17
- FWCI
- 51.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Natural Science Foundation of China (81421001, 81320108024, 81530072, 81522008 31371273, 31371420, 81572303, 81001070)
- National Key Technology R&D Program (2014BAI09B05)
- Program for Professor of Special Appointment (Eastern Scholar No. 201268, 2015 Youth Eastern Scholar NO.QD2015003)
- Shanghai Institutions of Higher Learning, the Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant (20152512, 20161309)
- National Cancer Institute (CA211016)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- Fusobacterium nucleatum, colorectal cancer, chemoresistance, autophagy, gut microbiota, TLR4, MyD88, microRNA, innate immune signaling, chronic inflammation
- MeSH terms
- Gastrointestinal Microbiome, Capecitabine, Animals, Antineoplastic Agents, Autophagy, Neoplasm Transplantation, Recurrence, Colorectal Neoplasms, Fusobacterium nucleatum, Platinum Compounds, Drug Resistance, Neoplasm, MicroRNAs, Toll-Like Receptors, Mice, Tumor Microenvironment, Heterografts
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