PRMT5-PAK1 Signaling Participates in Metastasis and Is Associated With Poor Prognosis in Human Esophageal Carcinoma

Abstract

Background/aim: Protein arginine methyltransferase 5 (PRMT5), a member of the 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 serine/threonine protein kinase family member, is a cytoskeletal protein that plays a critical role in metastasis. We examined the expression of PRMT5 and PAK1 in esophageal squamous cell carcinoma (ESCC) and evaluated the correlation between PRMT5/p-PAK1 and both clinicopathological parameters and prognosis of ESCC patients.

Materials and methods: 106 tumor tissues collected from ESCC patients were assessed for PRMT5 and PAK1 expression using immunohistochemistry. Pearson's correlation and Kaplan-Meier analysis were used to estimate the correlation with the clinicopathological parameters and effect on patient survival. Western blot analysis was used to determine the PRMT5/p-PAK1 protein expression. The wound healing assay was performed to assess the effect of PRMT5 on the migration of ESCC cells.

Results: PRMT5 is upregulated in ESCC and the level of PRMT5 is correlated with metastasis and 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) but not total PAK1. Kaplan-Meier analysis showed that the OS of the subgroup of patients with PRMT5^high/p-PAK1^high is remarkably shorter than those of other subgroups (i.e., PRMT5^high/p-PAK1^low, PRMT5^low/p-PAK1^low and PRMT5^low/p-PAK1^high).

Conclusion: PRMT5-PAK1 signaling participates in ESCC metastasis and can predict patients' outcomes.

Keywords: PAK1; PRMT5; esophageal squamous cell carcinoma; metastasis; migration; phosphorylated-PAK1.