Community-based network analyses reveal emerging connectivity patterns of protein-protein interactions in murine melanoma secretome

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Zelanis, André [UNIFESP]
Francisquini, Rodrigo [UNIFESP]
Berton, Rafael [UNIFESP]
Soares, Sandro - University of Cambridge
Pessotti, Dayelle [UNIFESP]
Camacho, Maurício [UNIFESP]
Andrade-Silva, Débora - Instituto Butantan
Barcick, Uilla [UNIFESP]
Serrano, Solange - Instituto Butantan
Chammas, Roger - Universidade de São Paulo
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Protein-protein interaction networks (PPINs) are static representations of protein connections in which topological features such as subgraphs (communities) may contain proteins functionally related, revealing an additional layer of interactome complexity. We created two PPINs from the secretomes of a paired set of murine melanocytes (a normal melanocyte and its transformed phenotype). Community structures, identified by a graph clustering algorithm, resulted in the identification of subgraphs in both networks. Interestingly, the underlying structure of such communities revealed shared and exclusive proteins (core and exclusive nodes, respectively), in addition to proteins that changed their location within each community (rewired nodes). Functional enrichment analysis of core nodes revealed conserved biological functions in both networks whereas exclusive and rewired nodes in the tumoral phenotype network were enriched in cancer-related processes, including TGFβ signaling. We found a remarkable shift in the tumoral interactome, resulting in an emerging pattern which was driven by the presence of exclusive nodes and may represent functional network motifs. Our findings suggest that the rearrangement in the tumoral interactome may be correlated with the malignant transformation of melanocytes associated with substrate adhesion impediment. The interactions found in core and new/rewired nodes might potentially be targeted for therapeutic intervention in melanoma treatment.