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.

中文翻译：

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根据CXCL12的浓度，极光A在人胶质母细胞瘤细胞的迁移和存活中起着双重作用。

原发性胶质母细胞瘤是成人中最常见的人脑肿瘤，通常由于肿瘤复发而致命。我们以前证明胶质母细胞瘤起始细胞侵入脑室下区，并响应于CXCL12趋化因子的局部释放而促进其放射抗性。在这项工作中，我们表明有丝分裂的Aurora A激酶（AurA）通过CXCL12-CXCR4途径以ERK1 / 2依赖性方式被激活。此外，CXCL12-ERK1 / 2信号传导诱导AjuA的主要辅因子Ajuba的表达，从而允许AurA自身磷酸化。我们证明AurA有助于胶质母细胞瘤细胞存活，抗辐射，自我更新和增殖无论使用CXCL12进行外源刺激。另一方面，AurA在体外触发CXCL12介导的胶质母细胞瘤细胞迁移以及在异种移植实验中侵袭脑室下区。此外，AurA调节细胞骨架蛋白（即肌动蛋白和波形蛋白），并促进Rho-GTPase CDC42对CXCL12的促迁移活性。总之，这些结果表明，根据CXCL12的浓度，AurA（一种有丝分裂机制的众所周知的激酶）可能在人胶质母细胞瘤中扮演替代角色。