The Embryonic Key Pluripotent Factor NANOG Mediates Glioblastoma Cell Migration via the SDF1/CXCR4 Pathway

Int J Mol Sci. 2021 Sep 30;22(19):10620. doi: 10.3390/ijms221910620.


NANOG is a key transcription factor required for maintaining pluripotency of embryonic stem cells. Elevated NANOG expression levels have been reported in many types of human cancers, including lung, oral, prostate, stomach, breast, and brain. Several studies reported the correlation between NANOG expression and tumor metastasis, revealing itself as a powerful biomarker of poor prognosis. However, how NANOG regulates tumor progression is still not known. We previously showed in medaka fish that Nanog regulates primordial germ cell migration through Cxcr4b, a chemokine receptor known for its ability to promote migration and metastasis in human cancers. Therefore, we investigated the role of human NANOG in CXCR4-mediated cancer cell migration. Of note, we found that NANOG regulatory elements in the CXCR4 promoter are functionally conserved in medaka fish and humans, suggesting an evolutionary conserved regulatory axis. Moreover, CXCR4 expression requires NANOG in human glioblastoma cells. In addition, transwell assays demonstrated that NANOG regulates cancer cell migration through the SDF1/CXCR4 pathway. Altogether, our results uncover NANOG-CXCR4 as a novel pathway controlling cellular migration and support Nanog as a potential therapeutic target in the treatment of Nanog-dependent tumor progression.

Keywords: CXCR4; NANOG; cancer cell migration; cancer stem cell; glioblastoma.

MeSH terms

  • Animals
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Chemokine CXCL12 / metabolism*
  • Gene Knockdown Techniques
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • HEK293 Cells
  • Humans
  • Nanog Homeobox Protein / genetics
  • Nanog Homeobox Protein / metabolism*
  • Oryzias / embryology
  • Promoter Regions, Genetic
  • Receptors, CXCR4 / metabolism*
  • Signal Transduction / genetics*
  • Transfection


  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Receptors, CXCR4