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

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Title
Profiling of protein-protein interactions via single-molecule techniques predicts the dependence of cancers on growth-factor receptors
Author(s)
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
Publication Date
2018-04
Journal
NATURE BIOMEDICAL ENGINEERING, v.2, no.4, pp.239 - 253
Publisher
NATURE PUBLISHING GROUP
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. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
URI
https://pr.ibs.re.kr/handle/8788114/5288
ISSN
2157-846X
Appears in Collections:
Center for Nanomedicine (나노의학 연구단) > Journal Papers
Files in This Item:
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