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Discoidin domain receptor 1 regulates ErbB2/ErbB3 signaling in mammary epithelial cells

Andrés Martin Toscani1, Pablo Aguilera2,3, Federico Coluccio Leskow2

  • 1IQUIBICEN-CONICET y Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.

FEBS Letters
|October 21, 2022
PubMed

Insights

Discoidin domain receptor 1 (DDR1) physically interacts with ErbB2 receptor tyrosine kinase in breast cancer cells. This interaction suggests DDR1 modulates ErbB2/ErbB3 signaling, impacting mammary gland development and cancer progression.

Area of Science:

  • Cell biology
  • Molecular oncology
  • Receptor tyrosine kinases

Background:

  • ErbB2 receptor tyrosine kinase is crucial for mammary gland development and functions as a signaling platform.
  • Discoidin domain receptors (DDRs) are collagen receptor tyrosine kinases implicated in various physiological and pathological processes.
  • Both ErbB2 and DDR family members are involved in cell signaling pathways relevant to cancer.

Purpose of the Study:

  • To investigate the interaction between ErbB2 and DDR1 receptors in breast cancer cells.
  • To determine if DDR1 colocalizes with ErbB2 and if this is due to physical interaction.
  • To explore the coexpression patterns of these receptors in normal and cancerous mammary tissues.

Main Methods:

  • Cell culture of breast cancer cells.
  • Immunofluorescence microscopy to assess receptor colocalization.
  • Co-immunoprecipitation assays to confirm physical interaction.
  • Analysis of tissue samples (normal mammary gland vs. breast tumors).

Main Results:

  • DDR1 colocalizes with ErbB2 in membrane clusters in breast cancer cells, irrespective of their expression levels.
  • This spatial coexistence is driven by a direct physical interaction between DDR1 and ErbB2.
  • DDR1 and ErbB2 are coexpressed in the normal mammary gland but show altered expression in breast tumors.
  • DDR1 acts as a novel modulator of the ErbB2/ErbB3 signaling pathway.

Conclusions:

  • DDR1 physically interacts with ErbB2 in breast cancer cells, forming signaling platforms.
  • The interaction between DDR1 and ErbB2 suggests a role for DDR1 in regulating ErbB2-mediated signaling.
  • DDR1 represents a potential therapeutic target or biomarker in breast cancer, particularly concerning ErbB2/ErbB3 pathways.
Keywords:
ErbB2breast cancercell adhesion receptorsmembrane clusters

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