Dual-specificity phosphatase 5 suppresses ovarian cancer progression by inhibiting IL-33 signaling.

Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. Dual-specificity phosphatases (DUSPs) are proteins that are reported involved in carcinogenesis, but their roles in OC have not be extensively studied. Here, we found that DUSP5 is markedly down-regulated in OC tissues. We reanalyzed DUSP5 expression in OC using published microarray data from the Gene Expression Omnibus (GEO) database and found that patients with low DUSP5 expression have significantly shorter overall survival than those with high expression (P < 0.001). Down-regulation of DUSP5 in OC tissues was immunohistochemically confirmed in tissue microarrays containing 15 normal ovary tissue samples and 60 OC specimens. Functional studies suggest that DUSP5 silence facilitates cell proliferation, migration, and invasion of OC cells in vitro. DUSP5 over-expression inhibits cell proliferation but has no effect on OC cell migration or invasion. Mechanistically, silencing DUSP5 transcriptionally activates interleukin 33 (IL-33) expression and secretion. Blockage of IL-33 with a neutralizing anti-IL33 antibody attenuates the effect of DUSP5 silencing to promote cell proliferation, migration, and invasion. Moreover, recombinant IL-33 protein treatment dramatically promotes OC cell proliferation, migration, and invasion with DUSP5 over-expression. Our study provides proof of principle that DUSP5 down-regulation promotes proliferation, migration, and invasion of OC cells via activation of IL-33 signaling.