Signaling networks assembled by oncogenic EGFR and c-Met

Proceedings of the National Academy of Sciences of the United States of America
Ailan GuoMichael J Comb

Abstract

A major question regarding the sensitivity of solid tumors to targeted kinase inhibitors is why some tumors respond and others do not. The observation that many tumors express EGF receptor (EGFR), yet only a small subset with EGFR-activating mutations respond clinically to EGFR inhibitors (EGFRIs), suggests that responsive tumors uniquely depend on EGFR signaling for their survival. The nature of this dependence is not understood. Here, we investigate dependence on EGFR signaling by comparing non-small-cell lung cancer cell lines driven by EGFR-activating mutations and genomic amplifications using a global proteomic analysis of phospho-tyrosine signaling. We identify an extensive receptor tyrosine kinase signaling network established in cells expressing mutated and activated EGFR or expressing amplified c-Met. We show that in drug sensitive cells the targeted tyrosine kinase drives other RTKs and an extensive network of downstream signaling that collapse with drug treatment. Comparison of the signaling networks in EGFR and c-Met-dependent cells identify a "core network" of approximately 50 proteins that participate in pathways mediating drug response.

References

Dec 24, 1997·Current Topics in Microbiology and Immunology·A S Fanning, J M Anderson
Jun 17, 2000·Trends in Cell Biology·C C GarnerR L Huganir
Jul 6, 2002·Science·I Bernard Weinstein
Jul 31, 2004·Science·Raffaella SordellaJeffrey Settleman
Aug 18, 2004·Nature Biotechnology·Blagoy BlagoevMatthias Mann
Aug 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·William PaoHarold Varmus
Dec 14, 2004·Nature Biotechnology·John RushMichael J Comb
Jan 20, 2005·Molecular & Cellular Proteomics : MCP·April ThelemannJohn D Haley
Feb 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey A EngelmanLewis C Cantley
Apr 9, 2005·Virchows Archiv : an International Journal of Pathology·Young Hwa SoungSug Hyung Lee
May 18, 2005·Proceedings of the National Academy of Sciences of the United States of America·Eunice L KwakDaniel A Haber
Jun 28, 2005·Molecular & Cellular Proteomics : MCP·William M OldNatalie G Ahn
Nov 12, 2005·The New England Journal of Medicine·Ingo K MellinghoffPaul S Mischel
Feb 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Gromoslaw A SmolenDaniel A Haber
Dec 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gregory J RielyWilliam Pao

❮ Previous
Next ❯

Citations

Jul 24, 2008·Histochemistry and Cell Biology·Olivier De WeverGeert Berx
Sep 19, 2008·Planta·Yaroslav BlumePavel Dráber
Jul 24, 2012·Amino Acids·Claus Jørgensen, Marie Locard-Paulet
Jun 19, 2012·Cancer Metastasis Reviews·Frank J Lowery, Dihua Yu
Dec 25, 2010·Cell Biochemistry and Biophysics·Ole KjaerulffAnita Jung
Dec 21, 1993·Biochimica Et Biophysica Acta·L BarbieriF Stirpe
Sep 21, 2012·Chemical Reviews·Meggie HakimHossam Haick
May 26, 2011·Journal of Proteome Research·Shawna L OrganMing-Sound Tsao
Dec 17, 2008·Journal of Proteome Research·Peter J UlintzAlexey I Nesvizhskii
Apr 2, 2011·Cell Death and Differentiation·A FurlanF Maina
Aug 1, 2008·Nature·Daehyun BaekDavid P Bartel
Aug 20, 2010·Nature Reviews. Cancer·Walter Kolch, Andrew Pitt
Aug 25, 2010·Nature Reviews. Cancer·Samir Hanash, Ayumu Taguchi
Sep 26, 2013·Nature Reviews. Clinical Oncology·Roopma WadhwaJaffer A Ajani
May 31, 2008·Nature Reviews. Drug Discovery·Paolo M ComoglioLivio Trusolino
May 13, 2010·Nature Reviews. Molecular Cell Biology·Chunaram Choudhary, Matthias Mann
Nov 26, 2010·Nature Reviews. Molecular Cell Biology·Livio TrusolinoPaolo M Comoglio
Mar 23, 2011·Oncogene·A M DulakJ M Siegfried
May 5, 2011·Integrative Biology : Quantitative Biosciences From Nano to Macro·G S PatelT Ng
Sep 26, 2008·The New England Journal of Medicine·Roy S HerbstScott M Lippman
Sep 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Udayan GuhaHarold E Varmus
Jan 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Hsin Hsien YehJuri G Gelovani
Oct 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·Akiyoshi UezuScott H Soderling
Dec 8, 2011·Molecular & Cellular Proteomics : MCP·Matthew V MyersDaniel C Liebler
Aug 4, 2009·Molecular & Cellular Proteomics : MCP·Fanny DuboisCarol MacKintosh
Oct 20, 2009·Molecular & Cellular Proteomics : MCP·Paul A RudnickStephen E Stein
Jun 9, 2010·The Cancer Journal·Stephen LeongS Gail Eckhardt
Apr 5, 2012·Genes & Development·Jeremy S Logue, Deborah K Morrison
Aug 26, 2010·Science Signaling·Albrecht MoritzMichael J Comb

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.