Identification of pathological nodes in the protein-protein interaction network maps of triple negative breast cancer

Advances in sequencing technologies have facilitated the identification of molecular targets for numerous human diseases, including cancer. Protein-protein interaction (PPI) networks derived from large-scale molecular data sets provide a global picture of the cellular process underlying pathogenesis and disease progression. As is typical in PPI networks, there are a few proteins that are connected with other proteins with high degree acting as hub or hot-spot nodes. The dysfunction of such hot-spot nodes is associated with disease development and progression. Proteins have either single or multi reactive interfaces and studying the interface properties of cancer-related proteins promises to help elucidate their role in PPI networks. In this study we analyzed PPI networks in Triple Negative Breast Cancer (TNBC) to delineate the hot-spot nodes and the related reactive protein interfaces. We provide a detailed analysis of TNBC-related PPI interfaces and the topological properties of the network. Cancer-related proteins have a defined unique binding interface, which may indicate their specificity and affinity for the cancer-related interactions in the networks. In addition, cancer related proteins in the network tend to interact with their partners through distinct interfaces that are crucial for cellular pathogenicity. Such proteins form the nodes with higher essentiality in the network. The findings from this study point to new targets in the development of TNBC as well as the key binding surfaces of putative drug candidates.