P0035 N,N′-dinitrosopiperazine involvement in metastasis of nasopharyngeal carcinoma by mediation of protein phosphorylation

Abstract

Background N,N′-dinitrosopiperazine (DNP), with specificity for nasopharyngeal epithelium, is involved in metastasis of nasopharyngeal carcinoma (NPC), although the underlying mechanism of action is unclear. Methods To reveal the pathogenesis of DNP-involved metastasis, we used immunoprecipitation to identify DNP-mediated phosphoproteins and their function. Findings DNP-mediated NPC cell (6–10B) motility and invasion was confirmed. Twenty-seven phosphorylated-proteins were modulated at least 1.5-fold by DNP. Changes in the expression levels of selected proteins were verified by western-blot analysis. DNP mediated the phosphorylated expression of ezrin threonine 567, vimentin serine 55, stathmin serine 25, and stat3 serine 727. Furthermore, DNP-mediated metastasis through ezrin phosphorylation at threonine 567 was confirmed; DNP-mediated metastasis was decreased when ezrin at threonine 567 was mutated. Interpretation These findings provide a novel insight into DNP-induced NPC metastasis and may help achieve a better understanding of the mechanisms of prolific metastasis in NPC.