Protein arginine methyltransferase 5 regulates AKT activation via methylation to promote metastasis

Protein arginine methyltransferase 5 (PRMT5) generates the majority of cellular symmetric di3 methyl-arginine marks on histones and non-histone proteins, thereby regulates a wide range of physiological processes. Here, we report that PRMT5 mediated AKT methylation is required for its activation by phosphorylation. Furthermore, PRMT5 transcriptionally regulates EGFR expression. AKT/EGFR signaling controls the expression of EMT-TFs, thereby impact tumor cell migration and invasion. We show that a PRMT5 inhibitor blocks tumor cell metastasis to the liver, a common metastatic site for neuroblastomas. Collectively, our results indicate that PRMT5 inhibition may represent a novel therapeutic tool to prevent metastatic cancers.