title: Adhesion signaling promotes protease‑driven polyploidization of glioblastoma cells.
abstract: 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.
authors.affiliation: Cancer Research Center, Roseman University of Health Sciences, Las Vegas, NV, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Mercapide
authors.affiliation: Cancer Research Center, Roseman University of Health Sciences, Las Vegas, NV, USA.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Lorico
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D011003:Ploidies; D011485:Protein Binding; D015398:Signal Transduction; D015533:Transcriptional Activation; D014161:Transduction, Genetic
chemical_list: D016023:Integrins; D048049:Extracellular Signal-Regulated MAP Kinases; D010447:Peptide Hydrolases