A cutting-edge surfaceome approach to unveil key players in breast cancer.
(2016) 8th Annual Canadian National Proteomics Network Symposium “Proteomic Advances in Health and Diseases” — Location: Montreal, Canada (12.April.2016)
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- Authors
Aubert, Léo 
- Abstract
- Despite continuous efforts, breast cancer remains the leading cause of cancer-related death in women. Occurring respectively in 20-25% and 40% of breast tumors, ERBB2 amplification and PIK3CA activating mutations (E545K, H1047R) are among the most common genomic aberrations in human breast cancer. However, significant advances in therapies targeting HER2 and PI3K oncoproteins fail to demonstrate good efficacy, mainly due to tumor heterogeneity and the development of acquired resistance. To expand the treatment options for breast cancer, new targets are desperately needed. In this respect, the characterization of cell surface proteome (surfaceome) changes occurring in transformed cells is essential to identify novel targets for cancer therapy and diagnosis. Insights into the complexity of the surfaceome have been yet limited by the lack of suitable methodologies. Herein, we have optimized a state-of-the-art proteomics approach based on the labeling of cell surface proteins with biotin reagents, their subsequent purification with avidin chromatography, and quantification using label-free quantitative proteomics with liquid chromatography-tandem mass spectrometry (LC-MS/MS). We have employed this proteomics approach to identify secreted and plasma membrane proteins that are differentially expressed on the cell surface of several MCF-10A human mammary epithelial cell lines that reflect the initiation of breast cancer induced either by HER2 overexpression or PIK3CA mutations. Interestingly, our LC-MS/MS analyses identified over 200 cell surface proteins in MCF-10A overexpressing HER2 from which 35% were significantly upregulated compared with isogenic MCF-10A cells. This molecular description of the surface of ERBB2-transformed cells will allow to characterize new putative targets for breast tumors.
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Citations
Aubert, L., Nandagopal, N., Lavoie, G., & Roux, P. P. (2016). A cutting-edge surfaceome approach to unveil key players in breast cancer. 8th Annual Canadian National Proteomics Network Symposium “Proteomic Advances in Health and Diseases”, Montreal, Canada. https://hdl.handle.net/2078.5/26916