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Signaling Networks Regulating Metastatic Progression in Triple-Negative Breast Cancer

Zuzanna Senkowska1, Katarzyna Owczarek1, Karolina Niewinna1

  • 1Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland.

Cells
|May 13, 2026
PubMed

Insights

Triple-negative breast cancer (TNBC) is aggressive due to metastasis. Understanding key signaling pathways like PI3K/Akt and TGF-β is crucial for developing new treatments to combat TNBC spread.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype lacking ER, PR, and HER2 expression.
  • Limited therapeutic options and high metastatic potential contribute to TNBC mortality.
  • Metastasis in TNBC is driven by complex, interconnected molecular signaling networks.

Purpose of the Study:

  • To review molecular mechanisms of TNBC metastatic progression.
  • To emphasize signaling pathways regulating invasion, migration, and distant organ colonization.
  • To identify potential therapeutic targets for limiting TNBC metastasis.

Main Methods:

  • Literature review of current knowledge on TNBC metastasis.
  • Focus on key signaling pathways: PI3K/Akt, TGF-β, Wnt/β-catenin, NF-κB, Rho/ROCK.
  • Discussion of pathway roles in epithelial-mesenchymal transition, cytoskeletal remodeling, CSC phenotypes, and TME interactions.

Main Results:

  • Identified PI3K/Akt, TGF-β, Wnt/β-catenin, NF-κB, and Rho/ROCK as key regulators of TNBC metastasis.
  • Highlighted their roles in epithelial-mesenchymal transition, cell migration, and invasion.
  • Emphasized the importance of tumor-microenvironment interactions in metastatic progression.

Conclusions:

  • Deeper understanding of these signaling networks is essential for TNBC research.
  • These pathways represent potential targets for novel therapeutic strategies.
  • Effective strategies are needed to limit metastatic disease and improve outcomes for TNBC patients.
Keywords:
cancer stem cellsepithelial–mesenchymal transitionmetastasissignaling pathwaystriple-negative breast cancertumor microenvironment

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