Profiling of protein-protein interactions via single-molecule techniques predicts the dependence of cancers on growth-factor receptors
- Profiling of protein-protein interactions via single-molecule techniques predicts the dependence of cancers on growth-factor receptors
- 정철현; 이홍원; 최병산; 강한나; 김현우; 민아름; 차민권; 류지영; 박상우; 손진영; 신기혁; 윤미란; 한주연; 손민주; 정주호; 이승효; 임석아; 조병철; 윤태영
- Cancer; Single-molecule biophysics
- Issue Date
- Nature biomedical engineering
- VOL 2, NO 4-253
- 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.
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