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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
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.
Abstract:
ErbB2 is an important member of the ErbB family, which activates growth and proliferation signaling pathways. ErbB2 is often overexpressed in various malignancies, especially in breast cancer, and is a common target for anti-cancer drugs. Breast cancer is currently one of the leading mortality causes in women, and acquired resistance to ErbB2-targeted therapies is a major obstacle in its treatment. Thus, understanding ErbB2-mediated signaling is crucial for further development of anti-cancer therapeutics and disease treatment. Previously, we have reported that the ErbB receptors interact with the major nucleolar protein nucleolin. In addition to its function in the nucleoli of cells, nucleolin participates in various cellular processes at the cytoplasm and cell-surface. Deregulated nucleolin is frequently overexpressed on the membrane of cancer cells. Here, we show that nucleolin increases colony formation and anchorage-independent growth of ErbB2-overexpressing cells. Importantly, this enhanced tumorigenicity also occurs in human ErbB2-positive breast cancer patients; namely, nucleolin overexpression in these patients is associated with reduced patient survival rates and increased disease-risk. ErbB2-nucleolin complexes are formed endogenously in both normal and cancer cells, and their effect on tumorigenicity is mediated through activation of ErbB2 signaling. Accordingly, nucleolin inhibition reduces cell viability and ErbB2 activation in ErbB2-positive cancer cells.
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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