Related Experiment Video

Updated: Jul 23, 2025

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
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PRMT-1 and p120-Catenin as EMT Mediators in Osimertinib Resistance in NSCLC

Kavya Sri Racherla1, Katrina Dovalovsky1, Meet Patel1

  • 1Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.

Cancers
|July 14, 2023
PubMed

Insights

Osimertinib resistance in EGFR-mutant NSCLC involves epithelial-mesenchymal transition (EMT). PRMT-1 and p120-catenin upregulation drives this resistance, suggesting potential therapeutic targets for overcoming Osimertinib resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Osimertinib is a first-line therapy for EGFR-mutant Non-Small Cell Lung Cancer (NSCLC).
  • Acquired resistance to Osimertinib, often via C797S mutation or epithelial-mesenchymal transition (EMT), limits long-term efficacy.
  • Understanding resistance mechanisms is crucial for improving NSCLC treatment outcomes.

Purpose of the Study:

  • To investigate the role of PRMT-1 and p120-catenin in mediating Osimertinib resistance (OR) through EMT in NSCLC.
  • To explore potential biomarkers for Osimertinib resistance.

Main Methods:

  • Investigated gene and protein expression of PRMT-1, p120-catenin, and Kaiso factor in Osimertinib-resistant cells.
  • Utilized siRNA to knockdown p120-catenin and assessed its impact on OR efficacy and EMT markers (wound closure assay).
  • Correlated p120-catenin expression with smoking status in NSCLC patients.

Main Results:

  • Upregulation of PRMT-1, p120-catenin, and Kaiso factor was observed in Osimertinib-resistant cells.
  • p120-catenin knockdown significantly increased OR efficacy (45%) and reduced cell migration (wound closure).
  • Higher p120-catenin expression was found in current smokers compared to non-smokers and quit-smokers.

Conclusions:

  • PRMT-1 and p120-catenin play a significant role in mediating Osimertinib resistance through EMT in NSCLC.
  • PRMT-1 may promote EMT by methylating Twist-1 and upregulating p120-catenin.
  • p120-catenin is a potential biomarker for Osimertinib resistance, and smoking may influence its expression.
Keywords:
EMTNSCLCOsimertinibPRMT-1epidermal growth factor receptorp120-cateninreactive oxygen species (ROS)

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