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Updated: Apr 19, 2026

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

Kang Li1,2, Chang Liu1,2, Jun-Hui Yin1,2

  • 1Department of Breast Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China.

Apoptosis : an International Journal on Programmed Cell Death
|April 17, 2026
PubMed

Insights

Researchers discovered a new tumor-suppressive pathway in breast cancer involving GATA3, RFPL3, and ASK1. This axis inhibits cancer growth, migration, and metastasis, offering potential new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Breast cancer poses significant clinical challenges despite advances in management.
  • Novel biomarkers are crucial for improving breast cancer treatment outcomes.

Purpose of the Study:

  • To identify and characterize novel tumor-suppressive pathways in breast cancer.
  • To elucidate the molecular mechanisms underlying breast cancer progression and metastasis.

Main Methods:

  • Investigated the transcriptional regulation of RFPL3 by GATA3.
  • Analyzed the role of RFPL3 in stabilizing and activating ASK1.
  • Examined the activation of the ASK1-JNK/p38 signaling cascade.
  • Assessed the impact of the GATA3-RFPL3-ASK1 axis on apoptosis, epithelial-mesenchymal transition (EMT), and cell invasion.

Main Results:

  • GATA3 directly activates RFPL3 transcription.
  • RFPL3 stabilizes and activates ASK1 through K63-linked polyubiquitination.
  • The ASK1-JNK/p38 signaling cascade activation induces apoptosis.
  • This cascade inhibits EMT and invadopodia formation, reducing cell migration and invasion.
  • The GATA3-RFPL3-ASK1 axis effectively suppresses breast cancer growth and lung metastasis in vivo.

Conclusions:

  • The GATA3-RFPL3-ASK1 axis represents a novel tumor-suppressive pathway in breast cancer.
  • This pathway holds potential as a therapeutic target for inhibiting breast cancer progression and metastasis.
Keywords:
ApoptosisBreast cancerGATA3MetastasisRFPL3

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