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FRK inhibits breast cancer cell migration and invasion by suppressing epithelial-mesenchymal transition

Yetunde Ogunbolude1, Chenlu Dai1, Edward T Bagu1,2

  • 1Department of Biochemistry, College of Medicine, University of Saskatchewan, Saskatoon, Canada.

Oncotarget
|January 20, 2018
PubMed

Insights

The human fyn-related kinase (FRK) acts as a tumor suppressor in breast cancer. Overexpressing FRK inhibits cancer cell growth, migration, and invasion by suppressing the epithelial-to-mesenchymal transition.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The human fyn-related kinase (FRK) is a non-receptor tyrosine kinase.
  • FRK exhibits tumor suppressor activity in breast cancer, but its mechanism is not fully understood.

Purpose of the Study:

  • To investigate the mechanism by which FRK suppresses breast cancer progression.
  • To identify FRK-regulated signaling pathways and molecular targets.

Main Methods:

  • Generated FRK-overexpressing MDA-MB-231 breast cancer cell lines.
  • Performed kinome analysis, immunoblotting, and RT-PCR.
  • Analyzed TCGA and GENT gene expression databases.

Main Results:

  • FRK overexpression suppressed proliferation, migration, and invasiveness.
  • FRK inhibited JAK/STAT, MAPK, and Akt signaling pathways.
  • FRK increased epithelial markers (E-cadherin) and decreased mesenchymal markers (vimentin, fibronectin, slug).
  • An inverse correlation was found between FRK expression and mesenchymal markers in breast cancer patients.

Conclusions:

  • FRK represses breast cancer cell proliferation, migration, and invasiveness.
  • FRK suppresses the epithelial-to-mesenchymal transition (EMT) pathway.
  • FRK functions as a suppressor of breast cancer metastasis.
Keywords:
STAT3basal A and Bbreast cancer subtypesfyn-related kinase -FRKtriple negative breast cancer

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