The expression of EMX2 lead to cell cycle arrest in glioblastoma cell line

BMC Cancer. 2018 Dec 4;18(1):1213. doi: 10.1186/s12885-018-5094-y.

Abstract

Background: Glioblastoma (GB) is a highly invasive primary brain tumor that nearly always systematically recurs at the site of resection despite aggressive radio-chemotherapy. Previously, we reported a gene expression signature related to tumor infiltration. Within this signature, the EMX2 gene encodes a homeodomain transcription factor that we found was down regulated in glioblastoma. As EMX2 is reported to play a role in carcinogenesis, we investigated the impact of EMX2 overexpression in glioma-related cell lines.

Methods: For that purpose, we constructed tetracycline-inducible EMX2 expression lines. Transfected cell phenotypes (proliferation, cell death and cell cycle) were assessed in time-course experiments.

Results: Restoration of EMX2 expression in U87 glioblastoma cells significantly inhibited cell proliferation. This inhibition was reversible after EMX2 removal from cells. EMX2-induced proliferative inhibition was very likely due to cell cycle arrest in G1/S transition and was not accompanied by signs of cell death.

Conclusion: Our results suggest that EMX2 may constitute a putative therapeutic target for GB treatment. Further studies are required to decipher the gene networks and transduction signals involved in EMX2's effect on cell proliferation.

Keywords: Cell cycle arrest; Cell proliferation; Glioblastoma - reversible phenotype; Transcriptome analysis.

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Cycle Checkpoints / physiology*
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Humans
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Tumor Cells, Cultured

Substances

  • Homeodomain Proteins
  • Transcription Factors
  • empty spiracles homeobox proteins