Proteomics of Triple-negative Breast Cancer

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SELECTBIO

Metodi Metodiev, Senior Lecturer/Director of Proteomics Unit, University of Essex

Abstract
Triple-negative breast cancer is hard to treat because of the lack of targeted therapeutic options. The malignant cells of this type express neither the steroid hormone receptors ER and PgR, nor ErbB2, making all existing targeted therapeutic options ineffective and inappropriate. This talk will present recent data obtained by genome-scale protein profiling of triple-negative tumors and SILAC-based phosphoroteomics of cultured cancer cells. The study found that CD74, a protein that is frequently overexpressed in epithelial cancers, is significantly overexpressed in the lymph node-positive tumors compared to less invasive node-negative tumors. Ectopic overexpression of CD74 in an established cancer cell line, which does not express the protein normally, resulted in stimulation of cell migration and significant increase of invasion through the extracellular matrix. Phosphoproteome analysis showed that CD74 overexpression causes changes in the phosphorylation of a multitude of signalling proteins. Specific changes in the cellular localization of proteins known to be involved in cancer progression and metastasis were also observed by confocal microscopy. The results and their implications will be discussed in the context of the emerging approaches for stratified/personalized treatment of cancer in general, and for the treatment of triple-negative breast cancer in particular.