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

• Published in: PloS one Vol. 8; no. 6; p. e68030
• Main Authors: Lee, Woo Sang, Woo, Eun Young, Kwon, Junhye, Park, Myung-Jin, Lee, Jae-Seon, Han, Young-Hoon, Bae, In Hwa
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.06.2013; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Active Transport, Cell Nucleus - physiology; AKT protein; Apoptosis Regulatory Proteins - metabolism; Bcl-2 protein; beta Catenin - metabolism; Biotechnology; Brain; Brain cancer; Brain tumors; Cancer; Cancer therapies; Cell Line, Tumor; Cell Movement - physiology; Cell Nucleus - metabolism; Cell Nucleus - pathology; Cell survival; Focal Adhesion Kinase 1 - metabolism; Gastric cancer; Gelatinase A; Gene expression; Glioblastoma; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastoma cells; Glioblastoma multiforme; Glioma; Humans; Immunoglobulins; Invasiveness; Laboratories; Lymphoma; Matrix Metalloproteinase 2 - metabolism; Medical prognosis; Medical research; Mesenchyme; Metastasis; Microscopy; Neoplasm Grading; Neoplasm Invasiveness - pathology; Neoplasm Invasiveness - physiopathology; Nuclear Proteins - metabolism; Nuclei (cytology); Phosphatidylinositol 3-Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Snail protein; Tissues; Transcription activation; Transcription factors; Tumor cell lines; Twist-Related Protein 1 - metabolism; Vimentin; Vimentin - genetics; Vimentin - metabolism; β-Catenin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068030

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.