The GluR2 subunit inhibits proliferation by inactivating Src-MAPK signalling and induces apoptosis by means of caspase 3/6-dependent activation in glioma cells

被引:32
作者
Beretta, Francesca [1 ,2 ]
Bassani, Silvia [2 ]
Binda, Elena [3 ]
Verpelli, Chiara [2 ,4 ]
Bello, Lorenzo [4 ]
Galli, Rossella [3 ]
Passafaro, Maria [1 ,2 ]
机构
[1] DTI Dulbecco Telethon Inst, I-20129 Milan, Italy
[2] Univ Milan, Dept Pharmacol, CNR, Inst Neurosci Cellular & Mol Pharmacol, I-20122 Milan, Italy
[3] Univ Milan, Dept Pharmacol, CNR, Inst Neurosci, I-20129 Milan, Italy
[4] Univ Milan, Neurosurg Unit, Fdn Ist Ricovero & Cura Carattere Sci, Osped Maggiore Policlin, I-20129 Milan, Italy
关键词
ERK1; 2; glioma specimens; GRIP; tumour stem cells; AMPA RECEPTOR SUBUNITS; HUMAN GLIOBLASTOMA; HIPPOCAMPAL-NEURONS; KINASE; PROTEIN; GROWTH; EXPRESSION; INTERACTS; NECROSIS; PATHWAY;
D O I
10.1111/j.1460-9568.2009.06804.x
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
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.
引用
收藏
页码:25 / 34
页数:10
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