Back to Search
Start Over
Ebastine impairs metastatic spread in triple-negative breast cancer by targeting focal adhesion kinase.
- Source :
-
Cellular & Molecular Life Sciences . May2023, Vol. 80 Issue 5, p1-14. 14p. - Publication Year :
- 2023
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1420682X
- Volume :
- 80
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Cellular & Molecular Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 163325793
- Full Text :
- https://doi.org/10.1007/s00018-023-04760-5