Reduction of Akt2 inhibits migration and invasion of glioma cells
Reduction of Akt2 inhibits migration and invasion of glioma cells
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Akt2 的减少抑制神经胶质瘤细胞的迁移和侵袭
DOI：
10.1002/ijc.24314
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发表时间：
2009-08-01
影响因子：
6.4
通讯作者：
Ma, Yongjie
中科院分区：
文献类型：
--
作者：
Zhang, Baogang;Gu, Feng;Ma, Yongjie
恶性神经胶质瘤有弥漫性侵入周围健康脑组织的倾向，从而妨碍其成功的手术切除。丝氨酸/苏氨酸激酶 Akt2 是众所周知的细胞存活和生长的重要调节因子。在这项研究中，我们发现 siRNA 介导的 Akt2 缺失抑制了神经胶质瘤细胞的迁移和侵袭。此外，我们还证明了 Akt2 促进细胞迁移和侵袭的机制。丝切蛋白的磷酸化（肌动蛋白聚合的关键步骤）和 Girdin 的磷酸化（对于肌动蛋白细胞骨架的完整性和细胞迁移至关重要）均受到损害。此外，表皮生长因子诱导的 ACAP1 磷酸化和整合素 β1 磷酸化也被阻断，这与粘附缺陷一致。因此，Akt2 在迁移过程中调节细胞粘附和细胞骨架重排。随后通过蛋白质印迹证实 Akt2 敲低的神经胶质瘤细胞中 MMP-9 表达降低，这与体外和体内侵袭减少一致。这些结果表明 Akt2 通过调节细胞骨架的形成、影响粘附和增加 MMP-9 的表达来促进胶质瘤细胞的迁移和侵袭。我们利用人胶质瘤组织切片进行的免疫组化结果也表明Akt2的表达与胶质瘤的恶性程度密切相关。这与我们的细胞系体内和体外结果一致。所有这些结果表明 Akt2 是神经胶质瘤侵袭的关键因素。这项研究确定 Akt2 是神经胶质瘤治疗干预的潜在抗侵袭靶点。 © 2009 UICC
Malignant gliomas have a tendency to invade diffusely into surrounding healthy brain tissues, thereby precluding their successful surgical removal. The serine/threonine kinase Akt2 is well known as an important regulator of cell survival and growth. In this study, we show that siRNA‐mediated depletion of Akt2 inhibited migration and invasion of glioma cells. In addition, we demonstrate the mechanisms by which Akt2 functions to promote cell migration and invasion. Phosphorylation of cofilin, a critical step of actin polymerization, and phosphorylation of Girdin, essential for the integrity of the actin cytoskeleton and cell migration, were impaired. Furthermore, epidermal growth factor‐induced ACAP1 phosphorylation and integrin β1 phosphorylation were also blocked, consistent with defects in adhesion. Thus, Akt2 regulates both cell adhesion and cytoskeleton rearrangement during migration. Decreased MMP‐9 expression in Akt2 knocked‐down glioma cells was subsequently confirmed by Western blotting, consistent with the decreased invasion in vitro and in vivo. These results suggest that Akt2 contributes to glioma cells migration and invasion by regulating the formation of cytoskeleton, influencing adhesion and increasing expression of MMP‐9. Our immunohistochemistry results by using human gliomas tissue sections also indicated that Akt2 expression was closely related with the malignancy of gliomas. This is coincident with our in vivo and in vitro results from cell lines. All of these results indicate that Akt2 is a critical factor in gliomas invasion. This study identifies that Akt2 is a potentially antiinvasion target for therapeutic intervention in gliomas. © 2009 UICC