The GluR2 subunit inhibits proliferation by inactivating Src-MAPK signalling and induces apoptosis by means of caspase 3/6-dependent activation in glioma cells
The GluR2 subunit inhibits proliferation by inactivating Src-MAPK signalling and induces apoptosis by means of caspase 3/6-dependent activation in glioma cells
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DOI：
10.1111/j.1460-9568.2009.06804.x
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发表时间：
2009-07-01
影响因子：
3.4
通讯作者：
Passafaro, Maria
中科院分区：
文献类型：
--
作者：
Beretta, Francesca;Bassani, Silvia;Passafaro, Maria
多形性胶质母细胞瘤（GBM）是最具侵袭性和未分化的脑肿瘤类型，因此手术干预无效。我们发现GluR 2在快速生长的GBM来源的肿瘤干细胞和高级别胶质瘤标本中不存在，但在缓慢生长的干细胞和低级别胶质瘤标本中表达。更值得注意的是，GluR 2在U-87 MG细胞中的过表达通过使细胞外信号调节激酶（ERK）1/2-Src磷酸化失活来抑制增殖并诱导凋亡。从机制上讲，我们观察到支架蛋白GRIP对于GluR 2对ERK-Src失活的影响是必不可少的。这些发现表明，GluR 2亚基的缺乏有利于恶性肿瘤。
Glioblastoma multiforme (GBM) is the most invasive and undifferentiated type of brain tumour, and so surgical interventions are ineffective. We found that GluR2 is absent in fast-growing GBM-derived tumour stem cells and high-grade glioma specimens, but is expressed in slow-growing stem cells and low-grade glioma specimens. More remarkably, GluR2 overexpression in U-87MG cells inhibits proliferation by inactivating extracellular signal-regulated kinase (ERK)1/2-Src phosphorylation and induces apoptosis. Mechanistically, we observed that the scaffold protein GRIP is essential for the effect of GluR2 on ERK-Src inactivation. These findings indicate that the absence of the GluR2 subunit favours malignancy.