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

Ting Qiu; Lei Hou; Lina Zhao; Xinye Wang; Zhongmei Zhou; Chuanyu Yang; Huifeng Zhang; Dewei Jiang; Baowei Jiao; Ceshi Chen

doi:10.1016/j.jbc.2023.105351

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

J Biol Chem. 2023 Nov;299(11):105351. doi: 10.1016/j.jbc.2023.105351. Epub 2023 Oct 12.

Authors

Ting Qiu¹, Lei Hou², Lina Zhao³, Xinye Wang⁴, Zhongmei Zhou⁴, Chuanyu Yang⁴, Huifeng Zhang⁵, Dewei Jiang⁶, Baowei Jiao⁷, Ceshi Chen⁸

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, 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, 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, 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: jiangdewei@mail.kiz.ac.cn.
⁷ Department of Breast Disease, Henan Breast Cancer Center, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China. Electronic address: jiaobaowei@mail.kiz.ac.cn.
⁸ 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; Academy of Biomedical Engineering, Kunming Medical University, Kunming, China; The Third Affiliated Hospital, Kunming Medical University, Kunming, China. Electronic address: chenc@mail.kiz.ac.cn.

Abstract

Breast cancer stem cells 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 breast cancer stem cells, partially through inhibiting the transcription of FGF-BP1, a secreted oncoprotein. Mechanistically, we demonstrate that SGCE could interact with the specific protein 1 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: TNBC; breast cancer stem cells; gene transcription; nuclear localization.

MeSH terms

Cell Line, Tumor
Cell Proliferation
Humans
Intercellular Signaling Peptides and Proteins / metabolism
Neoplastic Stem Cells* / metabolism
Sarcoglycans* / metabolism
Signal Transduction
Sp1 Transcription Factor* / metabolism
Triple Negative Breast Neoplasms* / metabolism

Substances

Sarcoglycans
SGCE protein, human
Sp1 Transcription Factor
FGFBP1 protein, human
Intercellular Signaling Peptides and Proteins