14-3-3ζ promotes gliomas cells invasion by regulating Snail through the PI3K/AKT signaling

Cancer Med. 2019 Feb;8(2):783-794. doi: 10.1002/cam4.1950. Epub 2019 Jan 18.

Abstract

14-3-3ζ has been reported to function as critical regulators of diverse cellular responses. However, the role of 14-3-3ζ in gliomas progression remains largely unknown. The expression level of 14-3-3ζ and Snail was detected by Western blot analysis and quantitative polymerase chain reaction in different grades of human gliomas. The effect of 14-3-3ζ on gliomas progression was measured using cell migration and invasion assay, the colony formation experiment, and CCK-8 assay. The effect of 14-3-3ζ on PI3K/AKT/Snail signaling protein expression levels was tested by Western blotting. Firstly, 14-3-3ζ was often up-regulated in high-grade gliomas relative to low-grade gliomas, and this overexpression was significantly related to tumor size, Karnofsky Performance Scale score and weaker disease-free survival. Secondly, the overexpression of 14-3-3ζ promoted gliomas cells proliferation, migration, and invasion. Conversely, the knockdown of 14-3-3ζ suppressed gliomas cells proliferation, migration, and invasion. Furthermore, subsequent mechanistic studies showed that 14-3-3ζ could activate PI3K/AKT/Snail signaling pathway to facilitate gliomas cells proliferation, migration, and invasion. This study shows that the overexpression of 14-3-3ζ can promote remarkably gliomas cells proliferation, migration, and invasion by regulating the Snail protein expression through activating PI3K/AKT signaling, and it may serve as a potential prognostic marker and therapeutic target for gliomas.

Keywords: 14-3-3ζ; PI3K/AKT; Snail; gliomas; invasion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • 14-3-3 Proteins / genetics
  • 14-3-3 Proteins / metabolism*
  • Animals
  • Brain / metabolism
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Female
  • Glioma / genetics
  • Glioma / metabolism*
  • Humans
  • Male
  • Mice, Nude
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism*

Substances

  • 14-3-3 Proteins
  • RNA, Messenger
  • Snail Family Transcription Factors
  • YWHAZ protein, human
  • Proto-Oncogene Proteins c-akt