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PMID: 17652589 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Ca2+-permeable AMPA receptors regulate growth of human glioblastoma via Akt activation.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 27 ·No. 30 ·2007-07-25 ·Pages 7987-8001

Ishiuchi S, Yoshida Y, Sugawara K, Aihara M, Ohtani T, Watanabe T, Saito N, Tsuzuki K, Okado H, Miwa A, Nakazato Y, Ozawa S

Abstract

Evidence has been accumulated that glioblastoma cells release and exploit glutamate for proliferation and migration by autocrine or paracrine loops through Ca2+-permeable AMPA-type glutamate receptors. Here, we show that Ca2+ signaling mediated by AMPA receptor regulates the growth and motility of glioblastoma cells via activation of Akt. Ca2+ supplied through Ca2+-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 Ca2+-permeable AMPA receptor. In contrast, introduction of a constitutively active form of Akt rescued tumor cells from apoptosis induced by the conversion of Ca2+-permeable AMPA receptor to Ca2+-impermeable receptors by the delivery of GluR2 cDNA. Therefore, Akt functions as downstream effectors for Ca2+-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.

MeSH Terms
Animals Brain Neoplasms/genetics,metabolism,pathology Calcium/metabolism Calcium Signaling/genetics Cell Proliferation Glioblastoma/genetics,metabolism,pathology Humans Mice Mice, Nude Neoplasm Invasiveness Permeability Proto-Oncogene Proteins c-akt/genetics,metabolism Rats Receptors, AMPA/genetics,metabolism,physiology Tumor Cells, Cultured
Chemicals
Receptors, AMPA Proto-Oncogene Proteins c-akt Calcium
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Ishiuchi Shogo
Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. ishogo@showa.gunma-u.ac.jp
Yoshida Yukari
Sugawara Kenichi
Aihara Masanori
Ohtani Toshiyuki
Watanabe Takashi
Saito Nobuhito
Tsuzuki Keisuke
Okado Haruo
Miwa Akiko
Nakazato Yoichi
Ozawa Seiji
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.2180-07.2007
Email
ishogo@showa.gunma-u.ac.jp
Published
2007-07-25
Pages
7987-8001
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6672718
Subset
IM
External Links
PubMed source DOI: 10.1523/JNEUROSCI.2180-07.2007 PMC Full Text View journal details
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