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FOXM1 transcriptionally regulates expression of integrin β1 in triple-negative breast cancer

Zuhal Hamurcu1,2,3, Nermin Kahraman1, Ahmed Ashour1

  • 1Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 422, Houston, TX, 77030, USA.

Breast Cancer Research and Treatment
|April 1, 2017
PubMed
Abstract

Insights

Forkhead box M1 (FOXM1) directly regulates Integrin beta 1 (ITGB1) gene expression in triple-negative breast cancer. This FOXM1/ITGB1/FAK pathway is crucial for TNBC progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Triple-negative breast cancer (TNBC) is aggressive, characterized by metastasis and poor survival.
  • Forkhead box M1 (FOXM1) is overexpressed in TNBC and plays an oncogenic role.
  • Integrin beta 1 (ITGB1) is upregulated in invasive breast cancers, correlating with poor outcomes.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which FOXM1 drives oncogenic effects in TNBC.
  • To investigate the regulation of Integrin beta 1 (ITGB1) gene expression in TNBC.
  • To explore the role of the FOXM1 transcription factor in TNBC progression.

Main Methods:

  • Utilized normal breast epithelial (MCF10A) and TNBC cell lines (MDA-MB-231, BT-20, MDA-MB436).
  • Employed siRNA-based knockdown to inhibit ITGB1 expression, confirmed by RT-PCR and Western blot.
  • Used Chromatin Immunoprecipitation (ChIP) and luciferase reporter assays to confirm FOXM1 binding to the ITGB1 promoter.

Main Results:

  • Demonstrated direct binding of FOXM1 to the ITGB1 gene promoter.
  • Showed that FOXM1 transcriptionally regulates ITGB1 expression in TNBC cells.
  • Confirmed FOXM1's regulation of Integrin beta 1 and focal adhesion kinase (FAK) activity.

Conclusions:

  • FOXM1 directly regulates Integrin beta 1 gene expression.
  • The FOXM1/Integrin-β1/FAK axis is implicated in the progression of triple-negative breast cancer.
  • FOXM1 represents a potential therapeutic target for TNBC.
Keywords:
Breast cancerFAKFOXM1Integrin β1InvasionMetastasisOncogeneTNBCTranscription factorTreatmentTriple-negative breast cancersiRNA

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