Capn4 is a marker of poor clinical outcomes and promotes nasopharyngeal carcinoma metastasis via nuclear factor-κB-induced matrix metalloproteinase 2 expression.
Bottom Line: The patients with NPC displaying higher Capn4 had a significantly shorter overall survival (P = 0.002) and progression-free survival (P = 0.003).These events resulted from Capn4 downregulation were associated with reduced expression of matrix metalloproteinase 2 (MMP2), Snail, and Vimentin.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.
Affiliation: Department of Anatomy, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.Show MeSH
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Mentions: Nuclear factor-κB is known to be a downstream signaling pathway of Capn4 in promoting tumor cell migration, for example, in hepatoma.16 Whereas Capn4 is able to activate NF-κB in HeLa cells,32 NF-κB upregulates MMP2 expression to promote migration and invasion of HCC cells.33 To this end, we further examined whether Capn4 upregulates MMP2 via activation of NF-kB in NPC cells. Western blotting analysis revealed that Capn4 knockdown by siRNA dramatically decreased levels of phosphorylated p65, a critical component of NF-κB, compared to control siRNA. Conversely, ectopic expression of Capn4 increased p65 phosphorylation (Fig.5a). Moreover, the NF-κB inhibitor helenalin blocked MMP2 upregulation induced by ectopic expression of Capn4 (Fig.5b). Together, these findings argue that Capn4 induces MMP2 expression at least in part via activation of NF-κB in NPC cells.
Affiliation: Department of Anatomy, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.