Over-expression of tetraspanin 8 in malignant glioma regulates tumor cell progression
Over-expression of tetraspanin 8 in malignant glioma regulates tumor cell progression
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DOI：
10.1016/j.bbrc.2015.01.128
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发表时间：
2015-03-13
影响因子：
3.1
通讯作者：
Sun, Qing-Fang
中科院分区：
文献类型：
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作者：
Pan, Si-Jian;Wu, Yue-Bing;Sun, Qing-Fang
肿瘤细胞侵袭和增殖仍然是恶性胶质瘤患者死亡的首要原因。为了建立有效的治疗方法，必须确定这些过程中隐含的新靶标。四跨膜蛋白 8 (Tspn8) 与多种跨膜蛋白和/或胞质蛋白形成复合物，以调节多种重要的细胞功能。在本研究中，我们发现Tspn8在临床多种恶性胶质瘤组织中过表达，其表达水平与肿瘤分级相关。恶性胶质瘤细胞（U251MG 和 U87MG 系）中的 Tspn8 表达对于细胞增殖和迁移很重要。 siRNA 介导的 Tspn8 敲低显着降低了 U251MG 和 U87MG 细胞的体外增殖和迁移。同时，Tspn8沉默还增加了替莫唑胺（TMZ）的敏感性，并且通过Tspn8敲低实现了TMZ显着增加U251MG或U87MG细胞死亡和凋亡。我们观察到 Tspn8 在人类恶性胶质瘤组织和上述胶质瘤细胞中与激活的粘着斑激酶 (FAK) 形成复合物。这种络合似乎是 FAK 激活所必需的，因为 Tspn8 敲除抑制了 U251MG 和 U87MG 细胞中的 FAK 激活。这些结果证明Tspn8可能通过促进胶质瘤细胞的增殖、迁移和TMZ抵抗而参与胶质母细胞瘤的发病机制。因此，靶向Tspn8可能为恶性胶质瘤提供潜在的治疗干预。 (C) 2015 Elsevier Inc. 保留所有权利。
Tumor cell invasion and proliferation remain the overwhelming causes of death for malignant glioma patients. To establish effective therapeutic methods, new targets implied in these processes have to be identified. Tetraspanin 8 (Tspn8) forms complexes with a large variety of trans-membrane and/or cytosolic proteins to regulate several important cellular functions. In the current study, we found that Tspn8 was over-expressed in multiple clinical malignant glioma tissues, and its expression level correlated with the grade of tumors. Tspn8 expression in malignant glioma cells (U251MG and U87MG lines) is important for cell proliferation and migration. siRNA-mediated knockdown of Tspn8 markedly reduced in vitro proliferation and migration of U251MG and U87MG cells. Meanwhile, Tspn8 silencing also increased the sensitivity of temozolomide (TMZ), and significantly increased U251MG or U87MG cell death and apoptosis by TMZ were achieved with Tspn8 knockdown. We observed that Tspn8 formed a complex with activated focal adhesion kinase (FAK) in both human malignant glioma tissues and in above glioma cells. This complexation appeared required for FAK activation, since Tspn8 knockdown inhibited FAK activation in U251MG and U87MG cells. These results provide evidence that Tspn8 contributes to the pathogenesis of glioblastoma probably by promoting proliferation, migration and TMZ-resistance of glioma cells. Therefore, targeting Tspn8 may provide a potential therapeutic intervention for malignant glioma. (C) 2015 Elsevier Inc. All rights reserved.