Zhao Liming, Pang Aixia, Li Yunchun
Department of Nuclear Medicine, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
Department of Urology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
Oncol Lett. 2018 Sep;16(3):3955-3963. doi: 10.3892/ol.2018.9134. Epub 2018 Jul 11.
Histone acetyltransferase GCN5 is a critical component of the TGF-β/Smad signaling pathway in breast cancer cells; however, it remains unknown whether it is involved in the development and progression of breast cancer. The present study investigated the role of GCN5 in the induction of the EMT by TGF-β1 in breast cancer cells and its underlying molecular mechanism of action. GCN5 activity was elevated and GCN5 mRNA expression and protein expression were increased in MDA-MB231 cells following stimulation with TGF-β1. Furthermore, TGF-β1 stimulation decreased expression of the epithelial cell marker E-cadherin and increased expression of the mesenchymal cell markers, N-cadherin and vimentin, as well as the expression of other EMT markers, including snail and slug. However, these changes were reversed following GCN5 knockdown leading to the downregulation of GCN5 expression. GCN5 knockdown also inhibited the viability, migration and invasion of MDA-MB231 cells, decreased the expression of p-STAT3, p-AKT, MMP9 and E2F1, and increased the expression of p21 in MDA-MB231 cells compared with cells stimulated with TGF-β1 alone. Therefore, GCN5 may work downstream of TGF-β/Smad signaling pathway to regulate the EMT in breast cancer.
组蛋白乙酰转移酶GCN5是乳腺癌细胞中TGF-β/Smad信号通路的关键组成部分；然而，其是否参与乳腺癌的发生发展仍不清楚。本研究探讨了GCN5在TGF-β1诱导乳腺癌细胞上皮-间质转化（EMT）中的作用及其潜在的分子作用机制。用TGF-β1刺激MDA-MB231细胞后，GCN5活性升高，GCN5 mRNA表达和蛋白表达增加。此外，TGF-β1刺激降低了上皮细胞标志物E-钙黏蛋白的表达，增加了间充质细胞标志物N-钙黏蛋白和波形蛋白的表达，以及其他EMT标志物（包括蜗牛蛋白和蛞蝓蛋白）的表达。然而，在GCN5基因敲低导致GCN5表达下调后，这些变化发生了逆转。与仅用TGF-β1刺激的细胞相比，GCN5基因敲低还抑制了MDA-MB231细胞的活力、迁移和侵袭，降低了p-STAT3、p-AKT、MMP9和E2F1的表达，并增加了MDA-MB231细胞中p21的表达。因此，GCN5可能在TGF-β/Smad信号通路的下游发挥作用，以调节乳腺癌中的EMT。
