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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Cell host & microbe
2024
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39626677/ |
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Table of Contents:
- Campylobacter jejuni-derived cytolethal distending toxin promotes colorectal cancer metastasis. He, Zhen Yu, Jing Gong, Junli Wu, Jinjie Zong, Xuan Luo, Zhanhao He, Xiaowen Cheng, Wai Ming Liu, Yugeng Liu, Chen Zhang, Qiang Dai, Lei Ding, Tao Gao, Beile Gharaibeh, Raad Z Huang, Jinlin Jobin, Christian Lan, Ping Animals Bacterial Toxins Colorectal Neoplasms Campylobacter jejuni Humans Mice STAT3 Transcription Factor Neoplasm Metastasis Campylobacter Infections Janus Kinase 2 Matrix Metalloproteinase 9 Cell Line, Tumor Signal Transduction Disease Models, Animal Female 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.