Drug targets for tumorigenesis: Insights from structural analysis of EGFR signaling network
Journal of Biomedical Informatics, cilt.42, sa.2, ss.228-236, 2009 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 42 Sayı: 2
- Basım Tarihi: 2009
- Doi Numarası: 10.1016/j.jbi.2008.08.008
- Dergi Adı: Journal of Biomedical Informatics
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.228-236
- Anahtar Kelimeler: Drug target, Epidermal growth factor receptor, Graph theory, Network decomposition analysis, Signal transduction, Tumorigenesis
- Boğaziçi Üniversitesi Adresli: Evet
Özet
Deciphering the complex network structure is crucial in drug target identification. This study presents a framework incorporating graph theoretic and network decomposition methods to analyze system-level properties of the comprehensive map of the epidermal growth factor receptor (EGFR) signaling, which is a good candidate model system to study the general mechanisms of signal transduction. The graph theoretic analysis of the EGFR network indicates that it has small-world characteristics with scale-free topology. The employment of network decomposition analysis enlightened the system-level properties, such as network cross-talk, specific molecules in each pathway and participation of molecules in the network. Participating in a significant fraction of the fundamental paths connecting the ligands to the phenotypes, cofactor GTP and complex Gβ/Gγ were identified as "housekeeping" molecules, through which all pathways of EGFR network are cross-talking. c-Src-Shc complex is identified as important due to its role in all fundamental paths through tumorigenesis and being specific to this phenotype. Inhibitors of this complex may be good anti-cancer agents having very little or no effect on other phenotypes. © 2008 Elsevier Inc. All rights reserved.