14-3-3ζ promotes esophageal squamous cell carcinoma invasion by repressing S1PR2 protein expression through NF-κB signaling

14-3-3 zeta is overexpressed in several cancers, including esophageal squamous cell carcinoma (ESCC), and plays an important role in tumorigenesis. However, the mechanisms underlying its tumorigenesis remain unclear. Here we report that 14-3-3 zeta was upregulated in ESCC tumors, compared with adjacent normal tissues; 14-3-3 zeta levels were positively correlated with ESCC lymph node metastasis and recurrence. Overexpression of 14-3-3 zeta promoted the tumor growth and invasion of ESCC in vitro and in vivo, whereas depletion of 14-3-3 zeta suppressed these effects. Moreover, 14-3-3 zeta reduces expression of genes mediating S1P/S1PR2 signaling, and this effect is mediated through activation of NF-kappa B. Taken together, 14-3-3 zeta contributes to ESCC tumorigenesis and progression through repressing S1PR2 signaling and may act as a new therapeutic target for ESCC.