E3 ubiquitin ligase BCA2 promotes breast cancer stemness by up-regulation of SOX9 by LPS

  • Int J Biol Sci. 2024 Apr 29;20(7):2686-2697. doi: 10.7150/ijbs.92338.
Min Zheng  1  2 ,  Wenjing Liu  3 ,  Rou Zhang  1 ,  Dewei Jiang  1  2 ,  Yujie Shi  4 ,  Yingying Wu  5 ,  Fei Ge  5 ,  Ceshi Chen  1  2  3  6
Affiliations
  • 1. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China.
  • 2. Kunming College of Life Sciences, University of Chinese Academy of Sciences, Kunming, Yunnan, China.
  • 3. The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118, China.
  • 4. Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China.
  • 5. The First Affiliated Hospital, Kunming Medical University, Kunming, 650032, China.
  • 6. Academy of Biomedical Engineering, Kunming Medical University, Kunming, 650500, China.
PMID: 38725852 DOI: 10.7150/ijbs.92338
Abstract

Triple-Negative Breast Cancer (TNBC) is the most malignant subtype of Breast Cancer. Breast Cancer Stem Cells (BCSCs) are believed to play a crucial role in the carcinogenesis, therapy resistance, and metastasis of TNBC. It is well known that inflammation promotes stemness. Several studies have identified breast cancer-associated gene 2 (BCA2) as a potential risk factor for Breast Cancer incidence and prognosis. However, whether and how BCA2 promotes BCSCs has not been elucidated. Here, we demonstrated that BCA2 specifically promotes lipopolysaccharide (LPS)-induced BCSCs through LPS induced SOX9 expression. BCA2 enhances the interaction between myeloid differentiation primary response protein 88 (MyD88) and Toll-like Receptor 4 (TLR4) and inhibits the interaction of MyD88 with Deubiquitinase OTUD4 in the LPS-mediated NF-κB signaling pathway. And SOX9, an NF-κB target gene, mediates BCA2's pro-stemness function in TNBC. Our findings provide new insights into the molecular mechanisms by which BCA2 promotes Breast Cancer and potential therapeutic targets for the treatment of Breast Cancer.

Keywords
BCA2; Breast cancer stem cells; LPS; MyD88; SOX9.
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