Nucleolin-binding by ErbB2 enhances tumorigenicity of ErbB2-positive breast cancer
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Eya Wolfson1, Maria Goldenberg1, Shira Solomon1, Amit Frishberg2, Ronit Pinkas-Kramarski1
1Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, 69978, Israel
2Department of Cell Research and Immunology, Tel-Aviv University, Ramat-Aviv, 69978, Israel
Ronit Pinkas-Kramarski, email: firstname.lastname@example.org
Keywords: ErbB/HER family, nucleolin, tyrosine kinase, breast cancer, TCGA
Received: June 29, 2016 Accepted: August 01, 2016 Published: August 17, 2016
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.
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