A tumor-resident bacterium promotes cervical cancer progression through lysoPC-mediated c-Jun/c-Fos activation

Tumor-resident microbiota are identified as a critical modulator in the carcinogenesis and progression of cervical malignancies. However, the mechanisms linking these microbiota to cervical cancer remain poorly understood. In this study, we find that patients with cervical cancer exhibit increased microbiota diversity, characterized by eight distinct bacterial species that distinguish them from control subjects. Intratumoral or intravenous administration of an isolated strain, Gordonia polyisoprenivorans GP-2, derived from tumor-resident microbiota, significantly promotes the growth and metastasis of cervical cancer in mice. Further investigation reveals that GP-2 metabolizes host-derived choline to produce the bacterial metabolite lysophosphatidylcholine (lysoPC). We propose and validate the biosynthetic pathway for lysoPC in strain GP-2 and demonstrate that lysoPC activates the classical tumorigenic genes c-Jun/c-Fos using cervical tumor organoids derived from patients. These findings elucidate the mechanisms underlying microbiota-host crosstalk in cervical cancer and highlight a potential therapeutic target for intervening in tumor-resident bacteria.