Campylobacter jejuni-derived cytolethal distending toxin promotes colorectal cancer metastasis

Abstract

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. • Campylobacter jejuni is enriched in the primary tumors of metastatic CRC patients • C. jejuni promotes CRC metastasis in a cytolethal distending toxin (CDT)-dependent manner • CDT activates the JAK2/STAT3/MMP9 signaling pathway to promote CRC metastasis • C. jejuni translocates from the intestine to extraintestinal tumors, promoting metastasis Solid tumors harbor intracellular bacteria, but the physiological consequences of these intratumor microorganisms remain poorly understood. By studying primary CRC and metastatic tissues, He et al. discovered an enriched presence of intratumor Campylobacter , whose production of genotoxin accelerates tumor metastasis, offering insight into the role bacteria play in metastasis.