Aurora A plays a dual role in migration and survival of human glioblastoma cells according to the CXCL12 concentration
| Autor: | Willems, Estelle, Dedobbeleer, Matthias, Digregorio, Marina, Lombard, Arnaud, Goffart, Nicolas, Lumapat, Paul Noel, Lambert, Jeremy, Van den Ackerveken, Priscilla, Szpakowska, Martyna, Chevigné, Andy, Scholtes, Felix, Rogister, Bernard |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Cancer microenvironment
Receptors CXCR4 Cell Survival MAP Kinase Signaling System Article Target validation Mice Cell Movement Cell Line Tumor Lateral Ventricles Animals Humans Cell migration Neoplasm Invasiveness Phosphorylation Aurora Kinase A Cancer stem cells Brain Neoplasms LIM Domain Proteins biological factors Chemokine CXCL12 nervous system diseases Neoplasm Proteins body regions CNS cancer Enzyme Activation embryonic structures Heterografts biological phenomena cell phenomena and immunity Glioblastoma Protein Processing Post-Translational Signal Transduction |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | Primary glioblastoma is the most frequent human brain tumor in adults and is generally fatal due to tumor recurrence. We previously demonstrated that glioblastoma-initiating cells invade the subventricular zones and promote their radio-resistance in response to the local release of the CXCL12 chemokine. In this work, we show that the mitotic Aurora A kinase (AurA) is activated through the CXCL12–CXCR4 pathway in an ERK1/2-dependent manner. Moreover, the CXCL12–ERK1/2 signaling induces the expression of Ajuba, the main cofactor of AurA, which allows the auto-phosphorylation of AurA. We show that AurA contributes to glioblastoma cell survival, radio-resistance, self-renewal, and proliferation regardless of the exogenous stimulation with CXCL12. On the other hand, AurA triggers the CXCL12-mediated migration of glioblastoma cells in vitro as well as the invasion of the subventricular zone in xenograft experiments. Moreover, AurA regulates cytoskeletal proteins (i.e., Actin and Vimentin) and favors the pro-migratory activity of the Rho-GTPase CDC42 in response to CXCL12. Altogether, these results show that AurA, a well-known kinase of the mitotic machinery, may play alternative roles in human glioblastoma according to the CXCL12 concentration. |
| Databáze: | OpenAIRE |
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