A Short Region of Connexin43 Reduces Human Glioma Stem Cell Migration, Invasion, and Survival through Src, PTEN, and FAK

Stem Cell Reports. 2017 Aug 8;9(2):451-463. doi: 10.1016/j.stemcr.2017.06.007. Epub 2017 Jul 14.


Connexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here, we show that a cell-penetrating peptide based on CX43 (TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients. Consequently, TAT-Cx43266-283 reduced GSC motility, as analyzed by time-lapse microscopy, and strongly reduced their invasive ability. Interestingly, we investigated the effects of TAT-Cx43266-283 on freshly removed surgical specimens as undissociated glioblastoma blocks, which revealed a dramatic reduction in the growth, migration, and survival of these cells. In conclusion, a region of CX43 (amino acids 266-283) exerts an important anti-tumor effect in patient-derived glioblastoma models that includes impairment of GSC migration and invasion.

Keywords: FAK; PTEN; Src; connexin; glioma stem cell; invasion; migration.

MeSH terms

  • CSK Tyrosine-Protein Kinase
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Connexin 43 / chemistry
  • Connexin 43 / genetics
  • Connexin 43 / metabolism*
  • Connexin 43 / pharmacology
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Glioma / genetics
  • Glioma / metabolism*
  • Humans
  • Models, Biological
  • Neoplastic Stem Cells / metabolism*
  • PTEN Phosphohydrolase / metabolism*
  • Peptide Fragments / pharmacology
  • Recombinant Fusion Proteins / pharmacology
  • src-Family Kinases / metabolism*


  • Connexin 43
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • CSK Tyrosine-Protein Kinase
  • Focal Adhesion Protein-Tyrosine Kinases
  • src-Family Kinases
  • CSK protein, human
  • PTEN Phosphohydrolase