Susumu Ohya
Kyoto Pharmaceutical University, Japan
Title: Downregulation of Ca2+-activated Cl- channel TMEM16A by histone deacetylase inhibition in breast cancer cells
Biography
Biography: Susumu Ohya
Abstract
TMEM16A (also known as ANO1 or DOG1) was identified as a pore-forming subunit of the Ca2+-activated Cl- channel, and plays an important role in driving the amplification of 11q13 in many types of human cancer.TMEM16A is responsible for facilitating cell growth and metastasis of TMEM16A-expressing,HER2-positive breast cancer cells. Recently, we found a significant decrease in TMEM16A expression and its functional activity induced by vorinostat, a pan-histone deacetylase inhibitor (HDACi) in HER2-positive breast cancer cell line YMB-1. Both pharmacological blockade and siRNA-induced inhibition of HDAC3 elicited a large decrease in TMEM16A expression and its functional activity in YMB-1. Additionally, we recently found that genetic and pharmacological inhibition of TMEM16A is responsible for the regulation of HER2 expression. Taken together, TMEM16A is epigenetically regulated by HDAC inhibition and in malignancies with a frequent gene amplification of TMEM16A, HDAC3 inhibition exerts the suppressive effects on cancer cell viability via a downregulation of TMEM16A.