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

Arch Biochem Biophys. 2018 Apr 2:643:7-13. doi: 10.1016/j.abb.2018.02.009. Epub 2018 Feb 16.

Abstract

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.

Keywords: 14-3-3ζ; ESCC; S1PR2; Tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation*
  • Esophageal Squamous Cell Carcinoma / diagnosis
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness
  • Prognosis
  • Receptors, Lysosphingolipid / genetics*
  • Signal Transduction*
  • Sphingosine-1-Phosphate Receptors

Substances

  • 14-3-3 Proteins
  • NF-kappa B
  • Receptors, Lysosphingolipid
  • S1PR2 protein, human
  • Sphingosine-1-Phosphate Receptors