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Transitional cell carcinoma ofbladder(TCCB) is a common malignancy worldwide, and outcomes for patients with advanced bladder cancer remain poor.To study the pathogenesis of TCCB, we investigated roles of Phospholipase Cε(PLCε), a phosphoinositide-specific PLC regulated by small GTPases including Ras and Rap.We evaluated whether small hairpin RNA(shRNA) against PLCε inhibits cell metastasis in bladder cancer cell lines.mRNA expression of PLCε was examined in 30 pairs of fresh TCCBs and corresponding nontumor bladder tissues.Overexpression of PLCε was frequently observed in TCCB.Knockdown of PLCε expression was constructed by adenovirus-mediated RNA interference tools.Following infection, the shRNA successfully suppressed PLCε mRNA and protein expression.Knocking down of PLCε in BIU-87 and T24 cells inhibited cell invasion compared to control groups.Furthermore, this inhibition was characterized by decreased vascular endothelial growth factor(VEGF), matrix metalloproteinase 2(MMP2), MMP-9 and phospho-STAT3.Additional JAK/STAT3 inhibitor AG490 treatment showed that phospho-Stat3 protein expression was decreased significantly in bladder cancer cells.AG490 remarkably inhibited the invasiveness of BIU-87 and T24 cells, VEGF, MMP-2, and MMP-9 protein expression was also decreased.These observations indicate a role for PLCε in cell metastasis and may provide a potential therapeutic pathway for the treatment of bladder cancer.