Bcl-w Enhances Mesenchymal Changes and Invasiveness of Glioblastoma Cells by Inducing Nuclear Accumulation of beta-Catenin
- Authors
- Lee, Woo Sang; Woo, Eun Young; Kwon, Junhye; Park, Myung-Jin; Lee, Jae-Seon; Han, Young-Hoon; Bae, In Hwa
- Issue Date
- 27-Jun-2013
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.8, no.6
- Journal Title
- PLOS ONE
- Volume
- 8
- Number
- 6
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/11266
- DOI
- 10.1371/journal.pone.0068030
- ISSN
- 1932-6203
- Abstract
- 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, beta-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-GSK3 beta-beta-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 beta-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.
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