PRMT5 Promotes Esophageal Carcinoma Metastasis by Enhancing PAK1 Phosphorylation

Abstract

Abstract Background Protein arginine methyltransferase 5 (PRMT5), a member of protein arginine methyltransferases, is an enzyme catalyzing the methylation of arginine residuals of histones and non-histone proteins to serve as one of many critical posttranslational modifications (PTMs). Phosphorylated P21-activated kinase 1 (p-PAK1), a member of serine/threonine protein kinases family, is a cytoskeletal protein playing a critical role in metastasis. This study aimed to explore the potential therapeutic value of PRMT5 and p-PAK1 in esophageal squamous cell carcinoma (ESCC). Methods and results PRMT5 expression in 106 primary human ESCC tissues with their adjacent non-cancerous tissues was detected by immunohistochemistry (IHC). Cell migration was detected by wound healing assays. Finally, we evaluated the clinical significance of PRMT5 combined with PAK1 and p-PAK1 by IHC staining. PRMT5 is upregulated in ESCC and the level of PRMT5 is not only correlated with metastasis but also can serve as an independent prognostic factor for overall survival (OS). PRMT5 knockdown remarkably inhibited ESCC cell migration with concomitantly reduced levels of phosphorylated PAK1 (p-PAK1). IHC assay of human ESCC tissue revealed that the levels of PRMT5 are highly correlated with that of p-PAK1. Kaplan-Meier analysis showed that the OS of patients with PRMT5high/p-PAK1high are significantly shorter than the others (PRMT5high/p-PAK1low, PRMT5low/p-PAK1low, and PRMT5low/p-PAK1high). Conclusions Targeting the PRMT5-p-PAK1 axis is of potential values in ESCC stratification and treatment.