Related Experiment Video

Updated: Jan 27, 2026

Using Three-color Single-molecule FRET to Study the Correlation of Protein Interactions
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Using Three-color Single-molecule FRET to Study the Correlation of Protein Interactions

Published on: January 30, 2018

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

Hong-Won Lee1,2,3,4,5, Byoungsan Choi4, Han Na Kang6

  • 1School of Biological Sciences and Institute for Molecular Biology and Genetics, Seoul National University, Seoul, South Korea.

Nature Biomedical Engineering
|April 3, 2019
PubMed

Insights

Understanding protein interactions in cancer helps tailor therapies. This study reveals how epidermal growth factor receptor (EGFR) mutations alter signaling complexes, aiding prediction of targeted therapy response in cancers lacking specific mutations.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cancer involves genetic and epigenetic changes altering protein-protein interactions (PPIs).
  • Characterizing signaling complexes is crucial for developing targeted cancer therapies.
  • The human epidermal growth-factor receptor (HER) family plays a key role in various cancers.

Purpose of the Study:

  • To investigate how genetic alterations in cancer cells rewire cellular signaling pathways via PPIs.
  • To characterize signaling complexes of the HER family in specific cancers.
  • To explore the potential of PPI analysis for predicting targeted therapy response.

Main Methods:

  • Utilized single-molecule pull-down and co-immunoprecipitation techniques.
  • Analyzed cancer-specific signaling phenotypes, including post-translational modifications and downstream PPIs.
  • Employed co-immunoprecipitation profiling to screen for EGFR-dependent cancers.

Main Results:

  • Activating mutations in the epidermal growth-factor receptor (EGFR) gene promote large protein complex formation around mutant EGFR.
  • Mutant EGFR signaling showed reduced dependency on phosphotyrosine residues.
  • HER-family PPI strength correlated with cellular dependence on HER-family signaling in breast and lung adenocarcinomas.
  • Identified non-small-cell lung cancers responsive to EGFR-targeted inhibitors using co-immunoprecipitation profiling.

Conclusions:

  • The study demonstrates a method to characterize cancer signaling complexes and predict targeted therapy response.
  • Findings highlight the role of altered PPIs in mutant EGFR signaling and cancer cell dependence.
  • This approach may aid in selecting patients for targeted therapies, especially in cancers without actionable genomic mutations.

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