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Effects of ErbB2 overexpression on the proteome and ErbB ligand-specific phosphosignalling in mammary luminal epithelial cells

Worthington, J; Spain, G; Timms, JF; (2017) Effects of ErbB2 overexpression on the proteome and ErbB ligand-specific phosphosignalling in mammary luminal epithelial cells. Molecular & Cellular Proteomics , 16 (4) pp. 608-621. 10.1074/mcp.M116.061267. Green open access

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Abstract

Most breast cancers arise from luminal epithelial cells and 25-30% of these tumours overexpress the ErbB2/HER2 receptor which correlates with disease progression and poor prognosis. The mechanisms of ErbB2 signalling and the effects of its overexpression are not fully understood. Herein, SILAC expression profiling and phosphopeptide enrichment of a relevant, non-transformed, immortalized human mammary luminal epithelial cell model were used to profile ErbB2-dependent differences in protein expression and phosphorylation events triggered via EGFR (EGF treatment) and ErbB3 (HRG1β treatment) in the context of ErbB2 overexpression. Bioinformatics analysis was used to infer changes in cellular processes and signalling events. We demonstrate the complexity of the responses to oncogene expression and growth factor signalling and identify protein changes relevant to ErbB2-dependent altered cellular phenotype, in particular cell cycle progression and hyper-proliferation, reduced adhesion and enhanced motility. Moreover, we define a novel mechanism by which ErbB signalling suppresses basal interferon signalling that would promote the survival and proliferation of mammary luminal epithelial cells. Numerous novel sites of growth factor-regulated phosphorylation were identified that were enhanced by ErbB2 overexpression and we putatively link these to altered cell behaviour and also highlight the importance of performing parallel protein expression profiling alongside phosphoproteomic analysis.

Type: Article
Title: Effects of ErbB2 overexpression on the proteome and ErbB ligand-specific phosphosignalling in mammary luminal epithelial cells
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1074/mcp.M116.061267
Publisher version: http://dx.doi.org/10.1074/mcp.M116.061267
Language: English
Additional information: This is an open access article under the Creative Commons CC-BY license (https://creativecommons.org/licenses/by/4.0/)
Keywords: Adhesion, Breast cancer, EGF, ErbB2, Growth factors, HRGbeta1, Interferon, Phosphoproteins, SILAC, Signal Transduction
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer
URI: https://discovery.ucl.ac.uk/id/eprint/1540993
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