Inhibition of HDACs-EphA2 Signaling Axis with WW437 Demonstrates Promising Preclinical Antitumor Activity in Breast Cancer.

EBioMedicine
Tao ZhangZhengdong Cai

Abstract

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.

Citations

Jul 20, 2020·Journal of Experimental & Clinical Cancer Research : CR·Rui ChenYali Wang
Aug 20, 2020·Journal of Hematology & Oncology·Ta XiaoMin Su
Feb 13, 2021·International Journal of Molecular Sciences·Daniel PensoldGeraldine Zimmer-Bensch
Apr 20, 2021·JBMR Plus·David B VaughtDana Brantley-Sieders
May 9, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Ping ZhaoCeshi Chen
Jun 8, 2021·Cancer Biomarkers : Section a of Disease Markers·Ganbiao WangYongxiang Li
Jul 29, 2018·Cancer Letters·Ilias NikasStamatios Theocharis

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Methods Mentioned

BETA
Assay
transfection
PCR
Immunoprecipitation
ChIP
histone acetylation
flow cytometry
co-immunoprecipitation
Co-IP
acetylation

Software Mentioned

Image
Pro Plus

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