Ebastine impairs metastatic spread in triple-negative breast cancer by targeting focal adhesion kinase

Juyeon Seo, Minsu Park, Dongmi Ko, Seongjae Kim, Jung Min Park, Soeun Park, Kee Dal Nam, Lee Farrand, Jinsol Yang, Chaok Seok, Eunsun Jung, Yoon Jae Kim, Ji Young Kim, Jae Hong Seo

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

We sought to investigate the utility of ebastine (EBA), a second-generation antihistamine with potent anti-metastatic properties, in the context of breast cancer stem cell (BCSC)-suppression in triple-negative breast cancer (TNBC). EBA binds to the tyrosine kinase domain of focal adhesion kinase (FAK), blocking phosphorylation at the Y397 and Y576/577 residues. FAK-mediated JAK2/STAT3 and MEK/ERK signaling was attenuated after EBA challenge in vitro and in vivo. EBA treatment induced apoptosis and a sharp decline in the expression of the BCSC markers ALDH1, CD44 and CD49f, suggesting that EBA targets BCSC-like cell populations while reducing tumor bulk. EBA administration significantly impeded BCSC-enriched tumor burden, angiogenesis and distant metastasis while reducing MMP-2/-9 levels in circulating blood in vivo. Our findings suggest that EBA may represent an effective therapeutic for the simultaneous targeting of JAK2/STAT3 and MEK/ERK for the treatment of molecularly heterogeneous TNBC with divergent profiles. Further investigation of EBA as an anti-metastatic agent for the treatment of TNBC is warranted.

Original languageEnglish
Article number132
JournalCellular and Molecular Life Sciences
Volume80
Issue number5
DOIs
Publication statusPublished - 2023 May

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

Keywords

  • Breast cancer stem cells
  • Drug repurposing
  • Ebastine
  • FAK
  • Metastasis
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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