Upregulation of PNCK Promotes Metastasis and Mediates Angiogenesis Via NF-κB/VEGF Signaling Pathway in Nasopharyngeal Carcinoma

Abstract

\n Background: Previous studies suggest that pregnancy upregulated non-ubiquitous calmodulin kinase (PNCK) depletion represses proliferation and promotes apoptosis of nasopharyngeal carcinoma (NPC) cells. However, the underlying mechanism of the regulatory role of PNCK on NPC invasion and metastasis remains unclear. Methods: The PNCK expression level was detected in specimens of non-metastatic and metastatic NPC by mRNA sequencing and immunohistochemistry. The wound-healing and transwell assays were employed to explore the ability of PNCK-mediated cell migration and invasion. Xenograft tumour model was adopted for monitoring tumour progression and lung metastasis was assessed by tail vein injection. Zebrafish model was used to explore the potential action of PNCK on tumor angiogenesis. We used gene set enrichment analysis and correlation analysis for mechanical investigation. Results: Human metastatic NPC samples showed increased PNCK expression in both mRNA and protein levels. In vitro assay showed that shRNA mediated silencing of PNCK inhibited NPC cell migration and invasion, while PNCK overexpression enhanced the metastatic potential of NPC cells. Additionally, in vivo experiments revealed that overexpression of PNCK favored the metastatic foci formation in the lung and tumor angiogenesis. Consistently, a significant increase of metastatic nodules in lungs in mice and the vascular-labeled fluorescence signal of zebrafish inoculated with PNCK-overexpression cells compared to control group. Pathway analysis identified that the depletion of PNCK may inhibits NF-κB/VEGF signaling pathway in NPC.Conclusions: These findings reveal that PNCK knockdown could suppress tumor metastasis and angiogenesis by regulating NF-κB/VEGF signaling pathway in NPC, suggesting that PNCK may represent a therapeutic target for NPC individualized treatment.