Comparison of Cellular Transforming Activity of OCT4, NANOG, and SOX2 in Immortalized Astrocytes

DNA Cell Biol. 2017 Nov;36(11):1000-1009. doi: 10.1089/dna.2017.3889. Epub 2017 Sep 21.

Abstract

Embryonic stem cell factors-OCT4, NANOG, and SOX2-contribute to the maintenance of stem cell properties and malignant progression in various cancers, including glioblastoma. Although functional roles of each of these genes are well documented in stem cell and cancer biology, no study has directly compared their cellular transforming activity under same experimental conditions. In this study, we compared the cellular transforming activity of OCT4, NANOG, and SOX2 using human immortalized astrocytes cultured under serum-free stem cell culture conditions. We found that SOX2 exhibited the strongest transforming activities, such as cell proliferation, neurosphere formation, resistance to cytotoxic drug, and cell migration/invasion, which may be associated with the activation of the nuclear factor kappa B (NFκB) signaling pathway. Thus, OCT4, NANOG, and SOX2, known to be frequently activated in various cancers and cancer stem cells, may play a distinct role in the regulation of cellular transformation.

Keywords: NANOG; NFκB; OCT4; SOX2; astrocytes; cellular transformation.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytes / pathology*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Movement
  • Cell Proliferation
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Nanog Homeobox Protein / genetics
  • Nanog Homeobox Protein / metabolism*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors