TRPV4 通过 AKT/Rac1 信号促进胶质瘤细胞的迁移和侵袭。
TRPV4 promotes the migration and invasion of glioma cells via AKT/Rac1 signaling.
机构信息
Department of Neurosurgery, Daping Hospital, The Army Medical University, Chongqing, 400042, China.
Department of Neurosurgery, Daping Hospital, The Army Medical University, Chongqing, 400042, China.
出版信息
Biochem Biophys Res Commun. 2018 Sep 5;503(2):876-881. doi: 10.1016/j.bbrc.2018.06.090. Epub 2018 Jun 19.
Experimental evidence indicates a critical role of TRPV4 (Transient Receptor Potential Vanilloid 4) in controlling the cell migratory activity of multiple tumors. However, the oncogenic role of TRPV4 in glioma still remains elusive. In this study, we tried to investigate the oncogenic role of TRPV4 in glioma. We found that the expression levels of TRPV4 were upregulated in glioma and the high levels of TRPV4 indicated a worse prognosis in patients with glioma. TRPV4 was critical for glioma migration and invasion: activating TRPV4 by agonist GSK1016790 A enhanced glioma migration and invasion, while, the specific TRPV4 antagonist HC-067047 suppressed glioma migration and invasion. Mechanically, activated TRPV4 promoted the activation of Rac1 (Ras-related C3 botulinum toxin substrate 1) by targeting the AKT for phosphorylation, then enhanced glioma migration and invasion. All these results suggested that TRPV4 accelerates glioma migration and invasion through the AKT/Rac1 signaling, and TRPV4 might be considered as a potential target for glioma therapy.
实验证据表明 TRPV4（瞬时受体电位香草醛 4）在控制多种肿瘤的细胞迁移活性方面起着关键作用。然而，TRPV4 在神经胶质瘤中的致癌作用仍不清楚。在这项研究中，我们试图研究 TRPV4 在神经胶质瘤中的致癌作用。我们发现 TRPV4 的表达水平在神经胶质瘤中上调，并且 TRPV4 水平高表明神经胶质瘤患者的预后较差。TRPV4 对神经胶质瘤的迁移和侵袭至关重要：激动剂 GSK1016790A 激活 TRPV4 增强神经胶质瘤的迁移和侵袭，而特异性 TRPV4 拮抗剂 HC-067047 则抑制神经胶质瘤的迁移和侵袭。在机制上，激活的 TRPV4 通过靶向 AKT 进行磷酸化来促进 Rac1（Ras 相关 C3 肉毒杆菌毒素底物 1）的激活，从而增强神经胶质瘤的迁移和侵袭。所有这些结果表明，TRPV4 通过 AKT/Rac1 信号通路加速神经胶质瘤的迁移和侵袭，TRPV4 可能被认为是神经胶质瘤治疗的潜在靶点。
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