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Peptostreptococcus anaerobius promotes cervical cancer angiogenesis by upregulating SCD to activate ERK pathway
Yingxin Gong1, Guannan Zhou1, Yuanyuan Gu1
1Obstetrics and Gynecology Hospital of Fudan University, Shanghai Key Laboratory of Reproduction and Development, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200433, China.
Abstract:
Accumulating evidence indicates that virginal microbiota dysbiosis is a distinct feature of cervical cancer. As cervical lesions progress towards malignancy, the dominance of Lactobacillus species within the vaginal microbiota is progressively replaced by anaerobic bacteria, with Peptostreptococcus anaerobius (P. anaerobius) being a noticeable one. Despite this well-documented microbial shift, the precise functional role of P. anaerobius in cervical cancer development and progression has remained unclear. Our study demonstrated that P. anaerobius promoted cervical cancer cells proliferation and enhanced tube formation of human umbilical vein endothelial cells (HUVECs). Furthermore, we identified a significant upregulation of stearoyl-CoA desaturase 1 (SCD) following the introduction of P. anaerobius, leading to subsequent activation of the extracellular signal-regulated kinase (ERK) signaling pathway. Moreover, supplement with P. anaerobius failed to reverse the ERK1/2 inhibitor-induced suppression of the tube-formation. In vivo validation revealed that P. anaerobius exerted its influence on angiogenesis by regulating SCD expression and ERK pathway acvivation. Collectively, these findings reveal an oncogenic role of P. anaerobius in cervical cancer, mediated by the SCD-ERK signaling axis to drive angiogenesis. This work provides novel mechanistic insights into the contribution of vaginal microbiota to gynecologic malignancies.
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