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

Authors
 Hong-Won Lee  ;  Byoungsan Choi  ;  Han Na Kang  ;  Hyunwoo Kim  ;  Ahrum Min  ;  Minkwon Cha  ;  Ji Young Ryu  ;  Sangwoo Park  ;  Jinyoung Sohn  ;  Kihyuk Shin  ;  Mi Ran Yun  ;  Joo Yeun Han  ;  Min Ju Shon  ;  Cherlhyun Jeong  ;  Junho Chung  ;  Seung-Hyo Lee  ;  Seock-Ah Im  ;  Byoung Chul Cho  ;  Tae-Young Yoon 
Citation
 NATURE BIOMEDICAL ENGINEERING, Vol.2 : 239-253, 2018 
Journal Title
NATURE BIOMEDICAL ENGINEERING
Issue Date
2018
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.
Full Text
https://www.nature.com/articles/s41551-018-0212-3
DOI
10.1038/s41551-018-0212-3
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/167635
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