Beretta Francesca, Bassani Silvia, Binda Elena, Verpelli Chiara, Bello Lorenzo, Galli Rossella, Passafaro Maria
DTI Dulbecco Telethon Institute, Via Vanvitelli 32, Milan 20129, Italy.
Eur J Neurosci. 2009 Jul;30(1):25-34. doi: 10.1111/j.1460-9568.2009.06804.x. Epub 2009 Jun 25.
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.
多形性胶质母细胞瘤（GBM）是侵袭性最强且未分化的脑肿瘤类型，因此手术干预无效。我们发现，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GluR2，但在生长缓慢的干细胞和低级别胶质瘤标本中表达。更值得注意的是，U - 87MG细胞中GluR2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GluR2对ERK - Src失活的作用至关重要。这些发现表明GluR2亚基的缺失有利于肿瘤的恶性发展。
