AnnexinA5 promote glioma cell invasion and migration via the PI3K/Akt/NF-κB signaling pathway

J Neurooncol. 2018 Jul;138(3):469-478. doi: 10.1007/s11060-018-2818-4. Epub 2018 Mar 8.

Abstract

As an important member of the Annexins, AnnexinA5 has been attributed important functions in trophoblast membrane repair, anticoagulation and cellular signal transduction. Accumulated studies show that AnnexinA5 is closely associated with various types of carcinomas. However, the potential contribution of AnnexinA5 to glioma cancer progression remains unclear. In this study, we report that AnnexinA5 is significantly upregulated in both high-grade glioma samples and glioma cell lines. Moreover, overexpression of AnnexinA5 promotes cell migration and invasion in vitro and tumorigenicity of glioma cells in nude mice, while knockdown of AnnexinA5 manifests a repressive function during these cellular processes. Importantly, mechanistic studies further reveal that AnnexinA5 is an essential transcriptional target of Snail via activating the PI3K/Akt/NF-κB signaling pathway. Taken together, these findings suggest that AnnexinA5 or the PI3K/Akt/NF-κB pathway may be promising therapeutic molecules to eradicate glioma metastases.

Keywords: AnnexinA5; Glioma; PI3K/Akt/NF-Κb; Progression; Signaling pathway.

MeSH terms

  • Animals
  • Annexin A5 / genetics
  • Annexin A5 / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Central Nervous System Neoplasms / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / metabolism*
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness / physiopathology*
  • Neoplasm Transplantation
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Snail Family Transcription Factors / metabolism

Substances

  • Annexin A5
  • NF-kappa B
  • Snail Family Transcription Factors
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt