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  3. The RIG-I-like receptor signaling pathway triggered by Staphylococcus aureus promotes breast cancer metastasis

The RIG-I-like receptor signaling pathway triggered by Staphylococcus aureus promotes breast cancer metastasis

  • Int Immunopharmacol. 2024 Dec 5;142(Pt B):113195. doi: 10.1016/j.intimp.2024.113195.
Haile Zhao 1,  Linzhe Zhang 1,  Dongdong Du 1,  Lisu Mai 1,  Yaping Liu 2,  Morigen Morigen 3,  Lifei Fan 4
Affiliations

Affiliations

  • 1 Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, State Key Laboratory of Reproductive Regulation & Breeding of Grassland livestock, School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, PR China.
  • 2 Department of Gynecology and Obstetrics, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, PR China.
  • 3 Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, State Key Laboratory of Reproductive Regulation & Breeding of Grassland livestock, School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, PR China. Electronic address: morigenm@hotmail.com.
  • 4 Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, State Key Laboratory of Reproductive Regulation & Breeding of Grassland livestock, School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, PR China. Electronic address: lifei.fan@imu.edu.cn.
PMID: 39303544 DOI: 10.1016/j.intimp.2024.113195
Abstract

Host microbes are increasingly recognized as key components in various types of Cancer, although their exact impact remains unclear. This study investigated the functional significance of Staphylococcus aureus (S. aureus) in breast Cancer tumorigenesis and progression. We found that S. aureus invasion resulted in a compromised DNA damage response process, as evidenced by the absence of G1-phase arrest and Apoptosis in breast cells in the background of double strand breaks production and the activation of the ataxia-telangiectasia mutated (ATM)-p53 signaling pathway. The high-throughput mRNA Sequencing, bioinformatics analysis and pharmacological studies revealed that S. aureus facilitates breast cell metastasis through the innate immune pathway, particularly in Cancer cells. During metastasis, S. aureus initially induced the expression of RIG-I-like receptors (RIG-I in normal breast cells, RIG-I and MDA5 in breast Cancer cells), which in turn activated NF-κB p65 expression. We further showed that NF-κB p65 activated the CCL5-CCR5 pathway, contributing to breast cell metastasis. Our study provides novel evidence that the innate immune system, triggered by Bacterial infection, plays a role in bacterial-driven Cancer metastasis.

Keywords

Breast cancer metastasis; CCL5-CCR5; Double strand breaks; NF-κB; RIG-I-like receptors; S. aureus.

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