Nucleolin-binding by ErbB2 enhances tumorigenicity of ErbB2-positive breast cancer

Eya Wolfson1, Maria Goldenberg1, Shira Solomon1

  • 1Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, 69978, Israel.

Oncotarget
|August 20, 2016
PubMed

Insights

Nucleolin enhances tumor growth in ErbB2-positive breast cancer by activating ErbB2 signaling. Inhibiting nucleolin reduces cancer cell viability and ErbB2 activation, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • ErbB2 (human epidermal growth factor receptor 2) overexpression drives cancer growth and is a target for therapies.
  • Acquired resistance to ErbB2-targeted drugs remains a significant challenge in breast cancer treatment.
  • Nucleolin, a nucleolar protein, also functions in the cytoplasm and on the cell surface, with deregulated expression in cancer.

Purpose of the Study:

  • To investigate the role of nucleolin in ErbB2-mediated signaling and tumorigenicity.
  • To determine the clinical relevance of nucleolin overexpression in ErbB2-positive breast cancer patients.

Main Methods:

  • Investigated the interaction between ErbB2 receptors and nucleolin.
  • Assessed the impact of nucleolin on colony formation and anchorage-independent growth in ErbB2-overexpressing cells.
  • Analyzed nucleolin expression in patient samples and correlated it with survival rates and disease risk.

Main Results:

  • Nucleolin overexpression enhances colony formation and anchorage-independent growth in ErbB2-overexpressing cells.
  • Nucleolin overexpression in patients with ErbB2-positive breast cancer correlates with reduced survival and increased disease risk.
  • ErbB2-nucleolin complexes are formed endogenously, and nucleolin activates ErbB2 signaling to promote tumorigenicity.
  • Nucleolin inhibition decreases cell viability and ErbB2 activation in ErbB2-positive cancer cells.

Conclusions:

  • Nucleolin plays a critical role in promoting tumorigenicity in ErbB2-positive breast cancer.
  • The ErbB2-nucleolin interaction represents a potential therapeutic target for overcoming treatment resistance.
  • Targeting nucleolin may offer a novel strategy for treating ErbB2-positive malignancies.

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