Adhesion signaling promotes protease-driven polyploidization of glioblastoma cells
| Autor: | Aurelio Lorico, Javier Mercapide |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Transcriptional Activation
MAPK/ERK pathway Integrins Cell Integrin Bioinformatics Transduction Genetic Cell Line Tumor Cell Adhesion Genetics medicine Humans Neoplasm Invasiveness Extracellular Signal-Regulated MAP Kinases Integrin binding Ploidies biology business.industry food and beverages General Medicine Cell cycle Cell biology medicine.anatomical_structure Cell culture Cancer cell biology.protein Glioblastoma business Intracellular Peptide Hydrolases Protein Binding Signal Transduction |
| Zdroj: | International Journal of Molecular Medicine. 34:1365-1371 |
| ISSN: | 1791-244X 1107-3756 |
| DOI: | 10.3892/ijmm.2014.1913 |
| Popis: | An increase in ploidy (polyploidization) causes genomic instability in cancer. However, the determinants for the increased DNA content of cancer cells have not yet been fully elucidated. In the present study, we investigated whether adhesion induces polyploidization in human U87MG glioblastoma cells. For this purpose, we employed expression vectors that reported transcriptional activation by signaling networks implicated in cancer. Signaling activation induced by intercellular integrin binding elicited both extracellular signal‑regulated kinase (ERK) and Notch target transcription. Upon the prolonged activation of both ERK and Notch target transcription induced by integrin binding to adhesion protein, cell cultures accumulated polyploid cells, as determined by cell DNA content distribution analysis and the quantification of polynucleated cells. This linked the transcriptional activation induced by integrin adhesion to the increased frequency of polyploidization. Accordingly, the inhibition of signaling decreased the extent of polyploidization mediated by protease‑driven intracellular invasion. Therefore, the findings of this study indicate that integrin adhesion induces polyploidization through the stimulation of glioblastoma cell invasiveness. |
| Databáze: | OpenAIRE |
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