Bcl-w Enhances Mesenchymal Changes and Invasiveness of Glioblastoma Cells by Inducing Nuclear Accumulation of β-Catenin

PLoS One. 2013 Jun 27;8(6):e68030. doi: 10.1371/journal.pone.0068030. Print 2013.


Bcl-w a pro-survival member of the Bcl-2 protein family, is expressed in a variety of cancer types, including gastric and colorectal adenocarcinomas, as well as glioblastoma multiforme (GBM), the most common and lethal brain tumor type. Previously, we demonstrated that Bcl-w is upregulated in gastric cancer cells, particularly those displaying infiltrative morphology. These reports propose that Bcl-w is strongly associated with aggressive characteristic, such as invasive or mesenchymal phenotype of GBM. However, there is no information from studies of the role of Bcl-w in GBM. In the current study, we showed that Bcl-w is upregulated in human glioblastoma multiforme (WHO grade IV) tissues, compared with normal and glioma (WHO grade III) tissues. Bcl-w promotes the mesenchymal traits of glioblastoma cells by inducing vimentin expression via activation of transcription factors, β-catenin, Twist1 and Snail in glioblastoma U251 cells. Moreover, Bcl-w induces invasiveness by promoting MMP-2 and FAK activation via the PI3K-p-Akt-p-GSK3β-β-catenin pathway. We further confirmed that Bcl-w has the capacity to induce invasiveness in several human cancer cell lines. In particular, Bcl-w-stimulated β-catenin is translocated into the nucleus as a transcription factor and promotes the expression of target genes, such as mesenchymal markers or MMPs, thereby increasing mesenchymal traits and invasiveness. Our findings collectively indicate that Bcl-w functions as a positive regulator of invasiveness by inducing mesenchymal changes and that trigger their aggressiveness of glioblastoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Apoptosis Regulatory Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Nucleus / metabolism*
  • Cell Nucleus / pathology
  • Focal Adhesion Kinase 1 / metabolism
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Neoplasm Grading
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / physiopathology*
  • Nuclear Proteins / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Twist-Related Protein 1 / metabolism
  • Vimentin / genetics
  • Vimentin / metabolism
  • beta Catenin / metabolism*


  • Apoptosis Regulatory Proteins
  • BCL2L2 protein, human
  • Nuclear Proteins
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • Vimentin
  • beta Catenin
  • Phosphatidylinositol 3-Kinases
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Proto-Oncogene Proteins c-akt
  • MMP2 protein, human
  • Matrix Metalloproteinase 2