Mutation specific functions of EGFR result in a mutation-specific downstream pathway activation

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
Lale Erdem-EraslanPim J French

Abstract

Epidermal growth factor receptor (EGFR) is frequently mutated in various types of cancer. Although all oncogenic mutations are considered activating, different tumour types have different mutation spectra. It is possible that functional differences underlie this tumour-type specific mutation spectrum. We have determined whether specific mutations in EGFR (EGFR, EGFRvIII and EGFR-L858R) have differences in binding partners, differences in downstream pathway activation (gene expression and phosphoproteins), and have functional consequences on cellular growth and migration. Using biotin pulldown and subsequent mass spectrometry we were able to detect mutation specific binding partners for EGFR. Differential binding was confirmed using a proximity ligation assay and/or Western Blot for the dedicator of cytokinesis 4 (DOCK4), UDP-glucose glycoprotein glucosyltransferase 1 (UGGT1), MYC binding protein 2 (MYCBP2) and Smoothelin (SMTN). We also demonstrate that each mutation induces the expression of a specific set of genes, and that each mutation is associated with specific phosphorylation patterns. Finally, we demonstrate using stably expressing cell lines that EGFRvIII and EGFL858R display reduced growth and migration compared to EG...Continue Reading

References

Feb 28, 1998·The Journal of Biological Chemistry·M A AntonyakA J Wong
May 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Mirko H H SchmidtOliver Bögler
Nov 16, 2005·Gastroenterology·Petra NiessenGuillaume van Eys
Jul 11, 2006·Nature Reviews. Molecular Cell Biology·Ami Citri, Yosef Yarden
Oct 10, 2006·Experimental Cell Research·Kiyo HiramotoHironori Katoh
Jan 27, 2007·The International Journal of Biochemistry & Cell Biology·Michalis V KaramouzisAthanasios G Papavassiliou
Aug 8, 2007·Cellular Signalling·Roza ZandiHans Skovgaard Poulsen
Mar 21, 2008·Breast Cancer Research and Treatment·Ton van AgthovenLambert C J Dorssers
Feb 11, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Martin J van den BentThierry Gorlia
Jan 14, 2010·Genome Biology·Kumaran KandasamyAkhilesh Pandey
Jan 16, 2010·Human Mutation·Lonneke A M GravendeelPim J French
Apr 7, 2010·Cell Stem Cell·Debbie L C van den BergRaymond A Poot
Oct 19, 2010·Nucleic Acids Research·Simon A ForbesP Andrew Futreal
Jan 11, 2011·Journal of Proteome Research·Vaibhav ChumbalkarOliver Bogler
Mar 30, 2011·Annals of Neurology·Linda B C BraltenPim J French
Sep 20, 2012·Biochemical and Biophysical Research Communications·Catherine A VaughanSumitra Deb
Dec 4, 2012·Nucleic Acids Research·Andrew Chatr-AryamontriMike Tyers
Dec 13, 2012·Advances in Anatomic Pathology·Frank G SchaapJudith V M G Bovée
Aug 8, 2013·Nature Methods·Dattatreya MellacheruvuAlexey I Nesvizhskii
Oct 15, 2013·Cell·Cameron W BrennanUNKNOWN TCGA Research Network
Feb 11, 2014·Cellular Signalling·Masakazu KobayashiHironori Katoh
Apr 3, 2014·Cold Spring Harbor Perspectives in Biology·Mark A LemmonKathryn M Ferguson

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