TPX2 promotes glioma cell proliferation and invasion via activation of the AKT signaling pathway.
TPX2 promotes glioma cell proliferation and invasion via activation of the AKT signaling pathway.
复制标题
DOI：
10.3892/ol.2016.5371
复制
发表时间：
2016-12
期刊：
影响因子：
2.9
通讯作者：
Wang SS
中科院分区：
文献类型：
--
作者：
Gu JJ;Zhang JH;Chen HJ;Wang SS
多形性胶质母细胞瘤(GBM)是成人原发脑癌中最常见、最恶性的类型。与GBM相关的最常见的表型是细胞侵袭；然而，控制这一过程的分子机制尚不清楚。非洲爪哇类激肽蛋白2靶向蛋白(TPX2)是一种核蛋白，在细胞增殖和有丝分裂纺锤体组装中发挥作用。TPX2在多种恶性肿瘤中高表达，包括人类恶性星形细胞瘤。尽管有这一发现，但TPX2在人脑胶质瘤中的确切作用尚不清楚。本研究报告了TPX2在一些胶质瘤细胞系中的高表达。TPX2过表达促进细胞增殖，降低G0/G1期细胞比例，增加U251和U87细胞的侵袭力。过表达TPX2还可显著增强AKT的磷酸化，降低p21的表达，上调细胞周期蛋白D1和基质金属多肽酶(MMP9)的表达。在U251和U87细胞中，TPX2的敲除导致了与TPX2过表达后观察到的表型直接相反的表型。其中，TPX2基因敲除抑制了细胞增殖，增加了G0/G1期细胞比例，抑制了侵袭，降低了AKT磷酸化，降低了基质金属蛋白酶-9和细胞周期蛋白D1的表达，增加了p21的表达。AKT抑制剂IV在很大程度上复制了TPX2基因下调的作用。提示TPX2可能通过AKT信号途径促进胶质瘤细胞的增殖和侵袭。
Glioblastoma multiforme (GBM) is the most common and most malignant type of primary adult brain cancer. The most common phenotype associated with GBM is cellular invasion; however, the molecular mechanisms governing this process are poorly understood. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a nuclear protein with roles in cellular proliferation and mitotic spindle assembly. TPX2 is overexpressed in various malignancies, including human malignant astrocytoma. Despite this finding, the exact role of TPX2 in human glioma is not well defined. The present study reports the elevated expression of TPX2 in a number of glioma cell lines. TPX2 overexpression promoted cellular proliferation, decreased the percentage of cells in G0/G1 phase, and increased invasion of both U251 and U87 cells. Overexpression of TPX2 also significantly enhanced the phosphorylation of AKT, decreased the expression of p21, and increased the expression of cyclin D1 and matrix metallopeptidase (MMP)-9. In both U251 and U87 cells, knockdown of TPX2 resulted in phenotypes that are in direct contrast to those observed following TPX2 overexpression. Specifically, TPX2 knockdown inhibited cell proliferation, increased the percentage of cells in G0/G1 phase, inhibited invasion, decreased AKT phosphorylation, decreased the expression of MMP-9 and cyclin D1, and increased p21 expression. The AKT inhibitor IV in large part phenocopied the effect of TPX2 knockdown. The present data suggest that TPX2 promotes glioma cell proliferation and invasion via AKT signaling.