In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 27, No. 30 ( 2007-07-25), p. 7987-8001
Abstract:
Evidence has been accumulated that glioblastoma cells release and exploit glutamate for proliferation and migration by autocrine or paracrine loops through Ca 2+ -permeable AMPA-type glutamate receptors. Here, we show that Ca 2+ signaling mediated by AMPA receptor regulates the growth and motility of glioblastoma cells via activation of Akt. Ca 2+ supplied through Ca 2+ -permeable AMPA receptor phosphorylated Akt at Ser-473, thereby facilitating proliferation and mobility. A dominant-negative form of Akt inhibited cell proliferation and migration accelerated by overexpression of Ca 2+ -permeable AMPA receptor. In contrast, introduction of a constitutively active form of Akt rescued tumor cells from apoptosis induced by the conversion of Ca 2+ -permeable AMPA receptor to Ca 2+ -impermeable receptors by the delivery of GluR2 cDNA. Therefore, Akt functions as downstream effectors for Ca 2+ -signaling mediated by AMPA receptor in glioblastoma cells. The activation of the glutamate-AMPA receptor-Akt pathway may contribute to the high degree of anaplasia and invasive growth of human glioblastoma. This novel pathway might give an alternative therapeutic target.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.2180-07.2007
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2007
detail.hit.zdb_id:
1475274-8
SSG:
12
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