Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.12.246660v1?rss=1 Authors: Huang, L., Zhang, X.-O., Verdejo-Torres, O., Wigglesworth, K., Sun, X., Sallis, B., Moon, D., Huang, T., Rozen, E., Zhang, L., Wang, G., Shohet, J. M., Lee, M. M., Wu, J. Q. Abstract: Protein arginine methyltransferase 5 (PRMT5) generates most of the symmetric di-methyl-arginine marks on histones and non-histone proteins by which it regulates a wide range of physiological processes including cancer cell proliferation and metastasis. Here, we report that PRMT5 directly regulates epidermal growth factor receptor (EGFR) transcription and thus controls EGF stimulated EGFR signaling. PRMT5 modulates protein kinase B (AKT) activation by methylation of AKT1 Arg 15, which is required for its subsequent phosphorylation at AKT1 Thr 308 and Ser 473. The PRMT5/EGFR/AKT axis converges to regulate transcription factors ZEB1, SNAIL, and TWIST1 to promote the epithelial-mesenchymal transition (EMT), which supports tumor cell invasion and metastasis. Inhibiting PRMT5 methyltransferase activity with a small molecule inhibitor attenuated primary tumor growth and prevented hepatic metastasis in aggressive tumor models in vivo. Collectively, our results support the use of PRMT5 based therapies for metastatic cancer. Copy rights belong to original authors. Visit the link for more info