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Updated: Jan 24, 2026

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
11:34

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers

Published on: December 5, 2017

13.1K

PYK2 promotes HER2-positive breast cancer invasion

Shaymaa Ik Al-Juboori1,2, Jayakumar Vadakekolathu1, Sarra Idri1

  • 1The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK.

Journal of Experimental & Clinical Cancer Research : CR
|May 24, 2019
PubMed
Abstract

Insights

Metformin resistance in HER2+ breast cancer is linked to PYK2 activation, promoting invasion and reduced survival. This highlights the need to consider breast cancer heterogeneity for effective metformin therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Metformin, a common type 2 diabetes drug, shows potential in advanced cancer therapy.
  • However, breast cancer's heterogeneity impacts metformin response, activating pro-invasive pathways via focal adhesion kinase PYK2 in HER2+ cancers.

Purpose of the Study:

  • To investigate metformin's effect on diverse breast cancer cell lines.
  • To explore PYK2 activation and its role in metformin resistance, invasion, and survival in HER2+ breast cancer.
  • To assess PYK2's role in HER2+ breast cancer stem-like cells.

Main Methods:

  • In vitro proliferation, apoptosis, wound healing, and invasion assays.
  • Gene expression analysis (microarrays, qPCR), immunoblotting, and proteomic analyses.
  • Bioinformatic analysis of patient data (METABRIC study) and stem cell assays.

Main Results:

  • HER2+ breast cancer cells exhibit metformin resistance, associated with PYK2 activation.
  • PYK2 promotes invasion in metformin-resistant HER2+ cells and correlates with reduced patient survival.
  • PYK2 also plays a role in tumor initiation and invasion by HER2+ breast cancer stem-like cells.

Conclusions:

  • Metformin can drive invasion in HER2+ breast cancer via PYK2.
  • Therapeutic strategies using metformin must account for breast cancer's molecular heterogeneity to prevent chemoresistance, invasion, and recurrence.
Keywords:
Breast cancer stem cellsChemoresistanceMetforminPYK2/PTK2BPure HER2 breast Cancer

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