title: The GluR2 subunit inhibits proliferation by inactivating Src-MAPK signalling and induces apoptosis by means of caspase 3/6-dependent activation in glioma cells.
abstract: 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.
authors: DTI Dulbecco Telethon Institute, Via Vanvitelli 32, Milan 20129, Italy.
authors: Francesca
authors: F
authors: Beretta
authors: Silvia
authors: S
authors: Bassani
authors: Elena
authors: E
authors: Binda
authors: Chiara
authors: C
authors: Verpelli
authors: Lorenzo
authors: L
authors: Bello
authors: Rossella
authors: R
authors: Galli
authors: Maria
authors: M
authors: Passafaro
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism*; D053178:Caspase 6 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005910:Glioma / Q000503:physiopathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C491310:GRIP1 protein, human; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C505407:CASP3 protein, human; C505514:CASP6 protein, human; C505410:Casp3 protein, rat; C505518:Casp6 protein, rat; D053148:Caspase 3; D053178:Caspase 6; C104722:glutamate receptor ionotropic, AMPA 2