Preclinical ReportsTrichostatin A augments esophageal squamous cell carcinoma cells migration by inducing acetylation of RelA at K310 leading epithelia–mesenchymal transitionHuang, Kekea,,b,,*; Liu, Yuzhena,,b,,*; Gu, Chengweia,,b; Liu, Danhuia; Zhao, Baoshenga,,bAuthor Information aDepartment of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University bEsophageal Cancer Institute of Xinxiang Medical University cHenan Institute of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China * Dr. Keke Huang and Yuzhen Liu contributed equally to the writing of this article. Received 2 August 2019 Revised form accepted 22 February 2020 Correspondence to Baosheng Zhao, MD, Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China, Tel: +86 373 4404718; fax: +86 373 4402573; e-mail: email@example.com Anti-Cancer Drugs: July 2020 - Volume 31 - Issue 6 - p 567-574 doi: 10.1097/CAD.0000000000000927 Buy Metrics Abstract Protein acetylation modification controlled by acetyltransferases (HATs) and histone deacetylases (HDACs) regulates multiple biologic processes including cell proliferation and migration. HDAC inhibitors (HDACi) are currently used as a promising epigenetic-based therapy for cancer treatment. Of the anticancer activity, accumulating evidence has shown that HDACi can enhance cell migration in subset of cancer cells. Thus, there is a critical need to identify such counter anticancer activity to HDACi in different cancer cell types and elucidate the rational in order to develop appropriate combination therapies in cancer treatment. In seeking to address the effect of HDACi on esophageal squamous cell carcinoma (ESCC) cells migration, trichostatin A (TSA), a canonical HDACi targeting class I and class II HDACs, was used. Here, we report the discovery that TSA augmented ESCC cells migration by increasing the acetylation of nuclear factor-κB/RelA at lysine 310 (K310). To elucidate the mechanism by which TSA promotes the migration of ESCC cells, plasmid of RelA K310R, a mutant precluding acetylation at K310, was transfected into ESCC cells. Blocking acetylation of RelA at K310 significantly arrogated TSA-induced cell migration. Mechanistic investigations revealed that TSA increased the level of acetylated RelA at K310 (RelA K310ac), thereby increasing the level of epithelia–mesenchymal transition (EMT) transcription factor slug mRNA, which in turn induced EMT. Overall, this study indicates that TSA promotes ESCC cells migration by RelA K310ac-slug-EMT pathway. Our findings provide a strategy to eradicate HDACi-induced ESCC cells migration by targeting RelA as a combination therapy with nonspecific HDACi in ESCC treatment. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.