当前位置： SCI文献检索 > EUROPEAN JOURNAL OF PHARMACOLOGY期刊下所有文献 > Valproic acid promotes the epithelial-to-mesenchymal transition of breast cancer cells through stabilization of Snail and transcriptional upregulation of Zeb1.

Valproic acid promotes the epithelial-to-mesenchymal transition of breast cancer cells through stabilization of Snail and transcriptional upregulation of Zeb1.

Abstract：

:Histone deacetylases (HDACs) can regulate cancer progression and its inhibitors (HDACIs) have been widely used for cancer therapy. Valproic acid (VPA, 2-propylpentanoic acid) can inhibit the class I HDAC and suppress the malignancy of solid cancers. Our present study revealed that 1 mM VPA, which has no effect on cell proliferation, can significantly increase the migration and induce epithelial to mesenchymal transition (EMT) like properties of breast cancer cells. Further, VPA increased the expression of EMT-transcription factors (EMT-TFs) Snail and Zeb1. Knockdown of Snail and Zeb1 can attenuate VPA induced cell migration and EMT. Mechanistically, VPA increased the protein stability of Snail via suppression its phosphorylation at Ser 11. As to Zeb1, VPA can increase its promoter activity and transcription via a HDAC2 dependent manner. Over expression of HDAC2 can block VPA induced expression of Zeb1. Collectively, our data revealed that VPA can trigger the EMT of breast cancer cells via upregulation of Snail and Zeb1. It indicated that more attention should be paid to the effects of VPA on the clinical therapy of breast cancer.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Zhang S,Tang Z,Qing B,Tang R,Duan Q,Ding S,Deng D

doi

10.1016/j.ejphar.2019.172745

subject

Has Abstract

pub_date

2019-12-15 00:00:00

pages

172745

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(19)30697-1

journal_volume

865

pub_type

杂志文章

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