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<p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年4月17日

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  • Kang Li,
  • Chang Liu,
  • Jun-Hui Yin,
  • Yu-Ting He,
  • Zhi-Zhi Xu,
  • Wen-Jing Zhang,
  • Jian-Qi Wang,
  • Lu-Yao Hou,
  • Jing Feng,
  • Le-Min Lin,
  • Xiu-Qing Duan,
  • Yi Zhou,
  • Liang Ji

摘要

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.