Regulatory Network Motifs and Hotspots of Cancer Genes in a Mammalian Cellular Signaling Network

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Abstract

Mutations or overexpression of signaling genes can result in cancer development and metastasis. In this study, we manually assembled a human cellular Signaling network and developed a robust bioinformatics strategy for extracting cancer-associated single nucleotide polymorphisms (SNPs) using expressed sequence tags (ESTs). We then investigated the relationshipsof cancer-associated genes [cancer-associated SNP genes, known as cancer genes (CG) and cell mo-bility genes (CMGs)] in a signaling network context. Through a graph-theory-based analysis, we found that CGs are signi?cantly enriched in network hub proteins and cancer-associated genes are signi?cantly enriched or depleted in some particular network motif types. Furthermore, we identi?ed a substantial number of hotspots, the three- and four-node network motifs in which all nodes are either CGs or CMGs. More importantly, we uncovered that CGs are enriched in the convergent target nodes of most network motifs, although CMGs are enriched in the source nodes of most motifs. These results have implications for the foundations of the regulatory mechanisms of cancer development and metastasis.

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"Regulatory Network Motifs and Hotspots of Cancer Genes in a Mammalian Cellular Signaling Network," Journal of Cancer Therapy, Vol. 1 No. 1, 2009, pp. 28-35.

Conflicts of Interest

The authors declare no conflicts of interest.

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