Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Arch Biochem Biophys. 2018 Apr 2;643:7-13. doi: 10.1016/j.abb.2018.02.009. Epub 2018 Feb 16.
14-3-3ζ 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 14-3-3ζ was upregulated in ESCC tumors, compared with adjacent normal tissues; 14-3-3ζ levels were positively correlated with ESCC lymph node metastasis and recurrence. Overexpression of 14-3-3ζ promoted the tumor growth and invasion of ESCC in vitro and in vivo, whereas depletion of 14-3-3ζ suppressed these effects. Moreover, 14-3-3ζ reduces expression of genes mediating S1P/S1PR2 signaling, and this effect is mediated through activation of NF- κ B. Taken together, 14-3-3ζ contributes to ESCC tumorigenesis and progression through repressing S1PR2 signaling and may act as a new therapeutic target for ESCC.
14-3-3ζ 在多种癌症中过表达，包括食管鳞状细胞癌（ESCC），并在肿瘤发生中发挥重要作用。然而，其肿瘤发生的机制尚不清楚。在这里，我们报告 14-3-3ζ 在 ESCC 肿瘤中上调，与相邻的正常组织相比；14-3-3ζ 水平与 ESCC 淋巴结转移和复发呈正相关。14-3-3ζ 的过表达促进了 ESCC 的体外和体内肿瘤生长和侵袭，而 14-3-3ζ 的缺失则抑制了这些效应。此外，14-3-3ζ 降低了介导 S1P/S1PR2 信号的基因的表达，这种作用是通过 NF- κ B 的激活介导的。总之，14-3-3ζ 通过抑制 S1PR2 信号促进 ESCC 的肿瘤发生和进展，并且可以作为 ESCC 的新的治疗靶点。
