The GluR2 subunit inhibits proliferation by inactivating Src-MAPK signalling and induces apoptosis by means of caspase 3/6-dependent activation in glioma cells.
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.
Beretta
Francesca
F
DTI Dulbecco Telethon Institute, Via Vanvitelli 32, Milan 20129, Italy.
Bassani
Silvia
S
Binda
Elena
E
Verpelli
Chiara
C
Bello
Lorenzo
L
Galli
Rossella
R
Passafaro
Maria
M
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
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