Role of PTP1B in HER2 Signaling in Breast Cancer
Abstract:
The receptor tyrosine kinase ErbB2 is overexpressed in approximately 25 of all breast cancers. ErbB2, and the signaling pathways it activates, represent potential selective targets for therapy in breast cancer. However, drug resistance is a significant clinical problem with current ErbB2-targeted breast cancer therapies. This is because of our lack of understanding of the molecular mechanism underlying the role of ErbB2 in breast carcinogenesis. Recently, Dr. Chernoff and others have reported that a cytoplasmic enzyme, protein tyrosine phosphatase 1B PTP1B plays a positive role in ErbB2-induced breast cancer in vitro and in vivo. Therefore, a detailed understanding of the signaling crosstalk between ErbB2 and PTP1B regulated pathways is warranted. In this research proposal, I have aimed to identify key pro-oncogenic PTP1B regulated pathways in ErbB2 signaling in MCF10A breast epithelial cells using quantitative phosphoproteomics. This study has the potential to uncover novel molecular targets in ErbB2- positive breast cancer and is expected to provide new hope and direction to the present breast cancer biomarkers and therapeutics.