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Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

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Identification of novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted

Helen Creedon1, Laura Gómez-Cuadrado1, Žygimantė Tarnauskaitė1

  • 1Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.

Oncotarget
|February 18, 2016
PubMed

Insights

Resistance to HER2-targeted therapies in breast cancer can be overcome by targeting epithelial-to-mesenchymal transition (EMT). New strategies inhibiting Src and Axl kinases show promise for treating HER2-independent resistance in tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapies poses a significant challenge in treating HER2-positive breast cancer.
  • Understanding the mechanisms underlying this resistance is crucial for developing effective treatment strategies.

Purpose of the Study:

  • To identify molecular pathways associated with resistance to HER2-targeted therapies.
  • To investigate the role of epithelial-to-mesenchymal transition (EMT) in HER2-independent resistance.
  • To explore potential therapeutic targets for overcoming treatment resistance.

Main Methods:

  • Generation of HER2-positive breast cancer cell lines resistant to lapatinib or AZD8931.
  • Global proteomics analysis to identify EMT-associated proteins.
  • Prognostic analysis of EMT-associated genes in ERBB2-subtype breast cancers.
  • In vitro studies targeting Src and Axl kinases.

Main Results:

  • Acquired resistance to pan-HER kinase inhibitors was independent of HER2 and associated with EMT.
  • Proteomics identified novel EMT-associated proteins linked to HER2-independent resistance.
  • A subset of EMT-associated genes predicted prognosis in ERBB2-positive breast cancer.
  • Targeting Src and Axl kinases effectively inhibited proliferation in resistant cells.

Conclusions:

  • EMT is a key mechanism driving HER2-independent resistance to HER2-targeted therapies.
  • Specific EMT-associated proteins and genes are potential biomarkers for prognosis.
  • Inhibitors of Src and Axl kinases represent promising therapeutic options for overcoming resistance in HER2-positive breast cancer.
Keywords:
EMTHER2breast cancerproteomicsresistance

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