SGCE promotes breast cancer stemness by promoting the transcription of FGF-BP1 by Sp1

  • J Biol Chem. 2023 Oct 12:105351. doi: 10.1016/j.jbc.2023.105351.
Ting Qiu  1 ,  Lei Hou  2 ,  Lina Zhao  3 ,  Xinye Wang  4 ,  Zhongmei Zhou  4 ,  Chuanyu Yang  4 ,  Huifeng Zhang  5 ,  Dewei Jiang  6 ,  Baowei Jiao  7 ,  Ceshi Chen  8
Affiliations
  • 1. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Kunming, Yunnan, China; Kunming College of Life sciences, University of Chinese Academy Sciences, Kunming, Yunnan, China.
  • 2. Department of Breast Disease, Henan Breast Cancer Center, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China.
  • 3. Kunming College of Life sciences, University of Chinese Academy Sciences, Kunming, Yunnan, China; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
  • 4. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Kunming, Yunnan, China.
  • 5. Department of Clinical Pharmacy, the First People's Hospital of Yunnan Province/the Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China.
  • 6. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Kunming, Yunnan, China; Kunming College of Life sciences, University of Chinese Academy Sciences, Kunming, Yunnan, China. Electronic address: [email protected].
  • 7. Department of Breast Disease, Henan Breast Cancer Center, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China. Electronic address: [email protected].
  • 8. Academy of Biomedical Engineering, Kunming Medical University, Kunming 650500, China; The Third Affiliated Hospital, Kunming Medical University, Kunming 650118, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Kunming, Yunnan, China. Electronic address: [email protected].
PMID: 37838174 DOI: 10.1016/j.jbc.2023.105351
Abstract

Breast Cancer Stem Cells (BCSCs) are mainly responsible for poor prognosis, especially in triple-negative breast Cancer (TNBC). In a previous study, we demonstrated that ε-Sarcoglycan (SGCE), a type Ⅰ single-transmembrane protein, is a potential oncogene that promotes TNBC stemness by stabilizing EGFR. Here, we further found that SGCE depletion reduces BCSCs, partially through inhibiting the transcription of FGF-BP1, a secreted oncoprotein. Mechanistically, we demonstrate that SGCE could interact with the Sp1 transcription factor and translocate into the nucleus, which leads to an increase in the transcription of FGF-BP1 and the secreted FBF-BP1 activates FGF-FGFR signaling to promote Cancer cell stemness. The novel SGCE-Sp1-FGF-BP1 axis provides novel potential candidate diagnostic markers and therapeutic targets for TNBC.

Keywords
Breast cancer stem cells; TNBC; gene transcription; nuclear localization.
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