Drug targets for tumorigenesis: Insights from structural analysis of EGFR signaling network

Tekir S. D., ARĞA K. Y., Uelgen K. O.

JOURNAL OF BIOMEDICAL INFORMATICS, cilt.42, sa.2, ss.228-236, 2009 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Derleme
  • 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: Signal transduction, Epidermal growth factor receptor, Graph theory, Network decomposition analysis, Tumorigenesis, Drug target, EPIDERMAL-GROWTH-FACTOR, LIGAND-INDUCED INTERNALIZATION, CELL-CYCLE PROGRESSION, PROTEIN KINASE-1 PDK1, SRC TYROSINE KINASE, FACTOR RECEPTOR, ALPHA-ACTININ, SMALL-WORLD, B-CELL, APOPTOSIS
  • Marmara 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 ill 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 G beta/G gamma 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. (C) 2008 Elsevier Inc. All rights reserved.