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Updated: Feb 12, 2026

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

Published on: December 5, 2017

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PAI-1 induces Src inhibitor resistance via CCL5 in HER2-positive breast cancer cells

Hehui Fang1, Juan Jin1, Doudou Huang1

  • 1Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Cancer Science
|March 31, 2018
PubMed

Insights

We identified plasminogen activator inhibitor-1 (PAI-1) and chemokine (C-C motif) ligand 5 (CCL5) as key drivers of resistance to the Src inhibitor saracatinib in breast cancer. Targeting PAI-1 or CCL5 can overcome this resistance, offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Tyrosine kinase Src is implicated in breast cancer progression.
  • Src inhibitors show promise but face drug resistance challenges.
  • Saracatinib is an Src inhibitor used in breast cancer treatment.

Purpose of the Study:

  • To investigate the mechanisms of resistance to the Src inhibitor saracatinib in breast cancer.
  • To identify novel therapeutic targets for overcoming saracatinib resistance.

Main Methods:

  • Established a saracatinib-resistant breast cancer cell line (SKBR-3/SI).
  • Analyzed mRNA expression profiles to identify differentially expressed genes.
  • Utilized functional assays to assess the roles of PAI-1 and CCL5 in cell proliferation and migration.
  • Investigated the potential of targeting PAI-1 and CCL5 to reverse drug resistance.

Main Results:

  • Plasminogen activator inhibitor-1 (PAI-1) was significantly upregulated in resistant cells.
  • PAI-1 overexpression correlated with increased secretion of chemokine (C-C motif) ligand 5 (CCL5).
  • PAI-1 and CCL5 promoted breast cancer cell proliferation and migration.
  • Inhibition of PAI-1 or CCL5 reduced proliferation and migration in resistant cells.

Conclusions:

  • PAI-1 and CCL5 are crucial mediators of saracatinib resistance in breast cancer.
  • Targeting PAI-1 or CCL5 can reverse saracatinib resistance.
  • These findings suggest PAI-1 and CCL5 as potential therapeutic targets for overcoming resistance in clinical settings.
Keywords:
CCL5PAI-1Src inhibitorbreast cancerdrug resistance

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