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

Authors
  • Seo, Juyeon
  • Park, Minsu
  • Ko, Dongmi
  • Kim, Seongjae
  • Park, Jung Min
  • Park, Soeun
  • Nam, Kee Dal
  • Farrand, Lee
  • Yang, Jinsol
  • Seok, Chaok
  • Jung, Eunsun
  • Kim, Yoon-Jae
  • Kim, Ji Young
  • Seo, Jae Hong
Type
Published Article
Journal
Cellular and Molecular Life Sciences
Publisher
Springer-Verlag
Publication Date
Apr 25, 2023
Volume
80
Issue
5
Identifiers
DOI: 10.1007/s00018-023-04760-5
PMID: 37185776
PMCID: PMC10130003
Source
PubMed Central
Keywords
Disciplines
  • Original Article
License
Unknown

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. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-023-04760-5.

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