Journal
EBIOMEDICINE
Volume 31, Issue -, Pages 276-286Publisher
ELSEVIER
DOI: 10.1016/j.ebiom.2018.05.003
Keywords
HDACs; EphA2; WW437; Breast cancer; Growth; Metastasis
Funding
- NSFC [81502604, 81673304, 81702328]
- Shanghai Science and Technology Commission [14140904000, 15431902200]
- Shanghai Hospital Development Center [SHDC12013107]
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Histone deacetylase inhibitors (HDACi) are small molecules targeting epigenetic enzymes approved for hematologic neoplasms, which have also demonstrated clinical activities in solid tumors. In our present study, we screened our internal compound library and discovered a novel HDACi, WW437, with potent anti-breast cancer ability in vitro and in vivo. WW437 significantly inhibited phosphorylated EphA2 and EphA2 expression. Further study demonstrated WW437 blocked HDACs-EphA2 signaling axis in breast cancer. In parallel, we found that EphA2 expression positively correlates with breast cancer progression; and combined use of WW437 and an EphA2 inhibitor (ALW-II-41-27) exerted more remarkable effect on breast cancer growth than either drug alone. Our findings suggested inhibition of HDACs-EphA2 signaling axis with WW437 alone or in combination with other agents may be a promising therapeutic strategy for advanced breast cancer. (C) 2018 The Authors. Published by Elsevier B.V.
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