The GATA3-RFPL3-ASK1 axis suppresses breast cancer growth and lung metastasis

  • Apoptosis. 2026 Apr 17;31(4):127. doi: 10.1007/s10495-026-02335-w.
Kang Li  #  1  2 ,  Chang Liu  #  1  2 ,  Jun-Hui Yin  1  2 ,  Yu-Ting He  1  2 ,  Zhi-Zhi Xu  1  2 ,  Wen-Jing Zhang  1  2 ,  Jian-Qi Wang  3 ,  Lu-Yao Hou  1 ,  Jing Feng  1 ,  Le-Min Lin  1 ,  Xiu-Qing Duan  1 ,  Yi Zhou  4  5 ,  Liang Ji  6  7
Affiliations
  • 1. Department of Breast Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China.
  • 2. Key Laboratory of Hepatosplenic Surgery, Ministry of Education, No. 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China.
  • 3. Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China.
  • 4. Department of Breast Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China. [email protected].
  • 5. Key Laboratory of Hepatosplenic Surgery, Ministry of Education, No. 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China. [email protected].
  • 6. Department of Breast Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China. [email protected].
  • 7. Key Laboratory of Hepatosplenic Surgery, Ministry of Education, No. 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China. [email protected].
  • # Contributed equally.
PMID: 41995771 DOI: 10.1007/s10495-026-02335-w
Abstract

Despite the great improvements made in its clinical management during the past decades, breast Cancer remains a challenge with considerably high morbidity and mortality. Further efforts to explore new biomarkers with promising clinical potential are still needed nowadays. Collectively, our findings reveal the GATA3-RFPL3-ASK1 axis as a novel tumor-suppressive pathway in breast Cancer. Mechanistically, GATA3 transcriptionally activates RFPL3 by directly binding to its promoter. Subsequently, RFPL3 stabilizes and activates ASK1 via K63-linked polyubiquitination, which in turn activates the ASK1-JNK/p38 signaling cascade. The signaling cascade induces Apoptosis. Concurrently, this signaling cascade inhibits epithelial-mesenchymal transition (EMT) and invadopodia formation, thereby effectively inhibiting cell migration and invasion. The GATA3-RFPL3-ASK1 axis suppresses breast Cancer growth and lung metastasis in vivo.

Keywords
Apoptosis; Breast cancer; GATA3; Metastasis; RFPL3.
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