Campylobacter jejuni-derived cytolethal distending toxin promotes colorectal cancer metastasis
Various forms of solid tumors harbor intracellular bacteria, but the physiological consequences of these microorganisms are poorly understood. We show that Campylobacter is significantly enriched in primary colorectal cancer (CRC) lesions from patients with metastasis. Campylobacter jejuni-derived cytolethal distending toxin (CDT) promotes CRC metastasis through JAK2-STAT3-MMP9 signaling in liver or pulmonary metastatic mice models, as confirmed in C. jejuni-infected human colonic tissue and CDT-treated colonic tumoroids from patients. Genetic deletion of cdtB (ΔcdtB) or purified CdtB protein demonstrates that the genotoxin is essential for C. jejuni's pro-metastatic property. In C.-jejuni-colonized mice, increased translocation of CDT-producing C. jejuni to extraintestinal implanted tumors potentially leads to accelerated metastasis of these tumors. Overall, these findings demonstrate that an intratumor-bacteria-derived genotoxin accelerates tumor metastasis, potentially opening a new diagnostic and therapeutic avenue for cancer management.
Authors
- Tao Ding (ORCID: https://orcid.org/0000-0002-2200-0496)
- Yugeng Liu (ORCID: https://orcid.org/0000-0002-9769-9641)
- Junli Gong (ORCID: https://orcid.org/0000-0002-4732-055X)
- Zhanhao Luo (ORCID: https://orcid.org/0009-0001-7743-9850)
- Xuan Zong (ORCID: https://orcid.org/0000-0002-7856-1655)
- Christian Jobin (ORCID: https://orcid.org/0000-0002-3733-1001)
- Jinlin Huang (ORCID: https://orcid.org/0000-0001-9447-3666)
- Beile Gao (ORCID: https://orcid.org/0000-0002-5295-3415)
- Raad Z. Gharaibeh (ORCID: https://orcid.org/0000-0001-5484-8902)
- Chen Liu (ORCID: https://orcid.org/0009-0003-0430-6146)
- Zhen He (ORCID: https://orcid.org/0000-0001-8735-6672)
- Wu Jinjie
- Lei Dai (ORCID: https://orcid.org/0000-0002-7688-9817)
- Xiaowen He (ORCID: https://orcid.org/0009-0007-4465-0629)
- Wai Ming Cheng
- Ping Lan (ORCID: https://orcid.org/0000-0002-5225-5027)
- Jing Yu
- Qiang Zhang (ORCID: https://orcid.org/0000-0002-7882-5489)
Institutions
- Sun Yat-sen University (CN)
- University of Florida (US)
- Sixth Affiliated Hospital of Sun Yat-sen University (CN)
- South China Sea Institute Of Oceanology (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- Yangzhou University (CN)
- Florida College (US)
Publication Details
- Journal
- Cell Host & Microbe
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1016/j.chom.2024.11.006
- Citations
- 34
- Primary Topic
- Cancer Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 13.13
Funders
- National Natural Science Foundation of China
- Key Technologies Research and Development Program
- Science and Technology Planning Project of Guangdong Province