Aurora A plays a dual role in migration and survival of human glioblastoma cells according to the CXCL12 concentration

• Published in: Oncogene Vol. 38; no. 1; pp. 73 - 87
• Main Authors: 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
• Format: Journal Article Web Resource
• Language: English
• Published: England Nature Publishing Group 01.01.2019; Nature Publishing Group UK
• Subjects: Actin; Animals; aurora; Aurora Kinase A - physiology; Brain; Brain cancer; Brain Neoplasms - enzymology; Brain Neoplasms - pathology; Brain tumors; Care and treatment; Cdc42 protein; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Survival; Chemokine CXCL12 - pharmacology; Chemokine CXCL12 - physiology; Chemokines; CXCL12 protein; CXCR4 protein; Cytoskeletal proteins; Cytoskeleton; Development and progression; Enzyme Activation; Enzyme regulation; Extracellular signal-regulated kinase; Genetic aspects; Glioblastoma; Glioblastoma - enzymology; Glioblastoma - pathology; Glioblastoma cells; Glioblastomas; Gliomas; Guanine nucleotide-binding protein; Guanosine triphosphatases; Health aspects; Heterografts; Human health sciences; Human migration; Humans; Lateral Ventricles - pathology; LIM Domain Proteins - biosynthesis; LIM Domain Proteins - genetics; MAP Kinase Signaling System; Mice; Muscle proteins; Neoplasm Invasiveness; Neoplasm Proteins - physiology; Oncologie; Oncology; Phosphorylation; Phosphotransferases; Protein Processing, Post-Translational; Proteins; Receptors, CXCR4 - physiology; Recurrence (Disease); Sciences de la santé humaine; Signal Transduction; Subventricular zone; Tumors; Vimentin; Xenografts
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/s41388-018-0437-3

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.