2. Academic Validation
  3. SH3RF3 promotes breast cancer stem-like properties via JNK activation and PTX3 upregulation

SH3RF3 promotes breast cancer stem-like properties via JNK activation and PTX3 upregulation

  • Nat Commun. 2020 May 19;11(1):2487. doi: 10.1038/s41467-020-16051-9.
Peiyuan Zhang  # 1 2,  Yingjie Liu  # 1 2,  Cheng Lian 1,  Xuan Cao 3,  Yuan Wang 1,  Xiaoxun Li 1,  Min Cong 1,  Pu Tian 1,  Xue Zhang 1,  Gang Wei 3,  Tong Liu 4 5,  Guohong Hu 6
Affiliations

Affiliations

  • 1 Shanghai Institute of Nutrition and Health, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Chinese Academy of Sciences, Shanghai, China.
  • 2 CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 3 CAS Key Laboratory of Computational Biology, Collaborative Innovation Center for Genetics and Developmental Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
  • 4 Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China. [email protected].
  • 5 The Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin, China. [email protected].
  • 6 Shanghai Institute of Nutrition and Health, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Chinese Academy of Sciences, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 32427938 DOI: 10.1038/s41467-020-16051-9
Abstract

Cancer stem-like cells (CSCs) are the tumorigenic cell subpopulation and contribute to Cancer recurrence and metastasis. However, the understanding of CSC regulatory mechanisms remains incomplete. By transcriptomic analysis, we identify a scaffold protein SH3RF3 (also named POSH2) that is upregulated in CSCs of breast Cancer clinical tumors and Cancer cell lines, and enhances the CSC properties of breast Cancer cells. Mechanically, SH3RF3 interacts with the c-Jun N-terminal kinase (JNK) in a JNK-interacting protein (JIP)-dependent manner, leading to enhanced phosphorylation of JNK and activation of the JNK-JUN pathway. Further the JNK-JUN signaling expands CSC subpopulation by transcriptionally activating the expression of Pentraxin 3 (PTX3). The functional role of SH3RF3 in CSCs is validated with patient-derived organoid culture, and supported by clinical cohort analyses. In conclusion, our work elucidates the role and molecular mechanism of SH3RF3 in CSCs of breast Cancer, and might provide opportunities for CSC-targeting therapy.

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