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Updated: Aug 1, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer

Jing Bi1, Zhihui Wu1, Xin Zhang1,2

  • 1State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, 361102, Fujian, China.

Nature Communications
|April 24, 2023
PubMed

Insights

Triple-negative breast cancer (TNBC) progresses via EGFR monomer activating STAT3 when TMEM25 is low. Restoring TMEM25 inhibits this pathway, offering a potential targeted therapy for TNBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Triple-negative breast cancer (TNBC) has a poor prognosis and lacks targeted therapies.
  • Epidermal growth factor receptor (EGFR) overexpression is common in TNBC, but antibody-based targeting has shown limited efficacy.
  • The role of monomeric EGFR in TNBC progression is not well understood.

Purpose of the Study:

  • To investigate the role of monomeric EGFR and its interaction with STAT3 in TNBC.
  • To explore the function of transmembrane protein 25 (TMEM25) in EGFR signaling in TNBC.
  • To identify potential therapeutic strategies targeting the EGFR/STAT3 pathway in TNBC.

Main Methods:

  • Investigated EGFR monomer-mediated STAT3 activation in TNBC models.
  • Assessed the expression levels of TMEM25 in human TNBC samples.
  • Utilized adeno-associated virus (AAV) to deliver TMEM25 in preclinical TNBC models.
  • Analyzed STAT3 phosphorylation and TNBC progression in vivo.

Main Results:

  • EGFR monomer activates STAT3 in TNBC, particularly when TMEM25 expression is reduced.
  • Decreased TMEM25 facilitates EGFR monomer-mediated STAT3 phosphorylation independent of ligand binding.
  • Restoration of TMEM25 expression via AAV suppressed STAT3 activation and TNBC progression in mice.

Conclusions:

  • Monomeric EGFR signaling through STAT3 is a key driver of TNBC progression.
  • TMEM25 deficiency promotes TNBC by enabling aberrant EGFR-STAT3 activation.
  • TMEM25 repletion represents a promising therapeutic approach for TNBC.

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