These authors contributed equally to this work.
Capn4 is a marker of poor clinical outcomes and promotes nasopharyngeal carcinoma metastasis via nuclear factor-κB-induced matrix metalloproteinase 2 expression
Article first published online: 20 MAY 2014
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Volume 105, Issue 6, pages 630–638, June 2014
How to Cite
Cancer Sci 105 (2014) 630–638
National Natural Science Foundation of China (81302067). National Natural Science Foundation of Fujian Province (2012J05157).
- Issue published online: 4 JUN 2014
- Article first published online: 20 MAY 2014
- Accepted manuscript online: 7 APR 2014 02:34AM EST
- Manuscript Accepted: 3 APR 2014
- Manuscript Revised: 10 MAR 2014
- Manuscript Received: 6 DEC 2013
- National Natural Science Foundation of China. Grant Number: 81302067
- National Natural Science Foundation of Fujian Province. Grant Number: 2012J05157
- matrix metalloproteinase 2;
- nasopharyngeal carcinoma;
- nuclear factor-κB
Calpain small subunit 1 (Capn4) plays a key role in tumor migration or invasion. In this study, expression and function of Capn4 was investigated in human nasopharyngeal carcinoma (NPC). Here we report that both mRNA and protein levels of Capn4 were elevated in NPC tissues when compared to normal NP tissues. Similarly, Capn4 was also highly expressed in multiple NPC cell lines, compared to immortalized human nasopharyngeal epithelial cell line NP69. Moreover, expression of Capn4 was significantly correlated with Epstein-Barr virus infection, advanced stages, and lymph node or distant metastasis (P < 0.001). The patients with NPC displaying higher Capn4 had a significantly shorter overall survival (P = 0.002) and progression-free survival (P = 0.003). Furthermore, siRNA knockdown of Capn4 suppressed cell migration and invasion in vitro and in vivo. These events resulted from Capn4 downregulation were associated with reduced expression of matrix metalloproteinase 2 (MMP2), Snail, and Vimentin. Finally, we demonstrated that Capn4 upregulated MMP2 via nuclear factor-κB (NF-κB) activation, manifested by increased phosphorylation of p65, a subunit of NF-κB. Together, these findings argue a novel function of Capn4 in invasion and metastasis of NPC, and thereby suggest that Capn4 may represent an independent prognostic factor and a potential therapeutic target in NPC.