Protein arginine methyltransferase 1 coordinates the epithelial-mesenchymal transition/proliferation dichotomy in gastric cancer cells

Abstract

Protein arginine methyltransferase 1 (PRMT1) is up-regulated and promotes migration, invasion and proliferation in wide range of cancers. However, we for the first time identify that PRMT1 promotes migration and invasion and inhibits proliferation in gastric cancer cells, a phenomenon called "migration-proliferation dichotomy". First, we find that PRMT1 overexpression promotes migration and invasion and inhibits proliferation, whereas PRMT1 knockdown reverses the above abilities. Next, PRMT1 reduces the expression of epithelial marker E-cadherin and increases the expression of mesenchymal markers including N-cadherin, Vimentin, snail and β-catenin in gastric cancer cells. Furthermore, our studies show that PRMT1 silencing promotes the phosphorylation of LATS1, and then induces YAP phosphorylation, while overexpression of PRMT1 down-regulates the phosphorylation of LATS1 and YAP, indicating that PRMT1 inhibits EMT probably via Hippo signaling. Collectively, the present study reveals important roles of PRMT1 in progression of gastric cancer. Given the dual functions of PRMT1, it is as a potential drug target of gastric cancer with extreme caution.

Keywords: EMT; Gastric cancer; Hippo pathway; Migration-proliferation dichotomy; PRMT1.