Profiling of protein-protein interactions via single-molecule techniques predicts the dependence of cancers on growth-factor receptors

Title
Profiling of protein-protein interactions via single-molecule techniques predicts the dependence of cancers on growth-factor receptors
Authors
정철현이홍원최병산강한나김현우민아름차민권류지영박상우손진영신기혁윤미란한주연손민주정주호이승효임석아조병철윤태영
Keywords
Cancer; Single-molecule biophysics
Issue Date
2018-04
Publisher
Nature biomedical engineering
Citation
VOL 2, NO 4-253
Abstract
The accumulation of genetic and epigenetic alterations in cancer cells rewires cellular signalling pathways through changes in the patterns of protein– protein interactions (PPIs). Understanding these patterns may facilitate the design of tailored cancer therapies. Here, we show that single-molecule pull-down and co-immunoprecipitation techniques can be used to characterize signalling complexes of the human epidermal growth-factor receptor (HER) family in specific cancers. By analysing cancer-specific signalling phenotypes, including post-translational modifications and PPIs with downstream interactions, we found that activating mutations of the epidermal growth-factor receptor (EGFR) gene led to the formation of large protein complexes surrounding mutant EGFR proteins and to a reduction in the dependency of mutant EGFR signalling on phosphotyrosine residues, and that the strength of HER-family PPIs is correlated with the strength of the dependence of breast and lung adenocarcinoma cells on HER-family signalling pathways. Furthermore, using co-immunoprecipitation profiling to screen for EGFR-dependent cancers, we identified non-small-cell lung cancers that respond to an EGFR-targeted inhibitor. Our approach might help predict responses to targeted cancer therapies, particularly for cancers that lack actionable genomic mutations.
URI
http://pubs.kist.re.kr/handle/201004/67467
ISSN
2157-846X
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