Neuronal-driven glioma growth requires Gαi1 and Gαi3.
Theranostics
; 11(17): 8535-8549, 2021.
Article
em En
| MEDLINE
| ID: mdl-34373757
ABSTRACT
Neuroligin-3 (NLGN3) is necessary and sufficient to promote glioma cell growth. The recruitment of Gαi1/3 to the ligand-activated receptor tyrosine kinases (RTKs) is essential for mediating oncogenic signaling. Methods:
Various genetic strategies were utilized to examine the requirement of Gαi1/3 in NLGN3-driven glioma cell growth.Results:
NLGN3-induced Akt-mTORC1 and Erk activation was inhibited by decreasing Gαi1/3 expression. In contrast ectopic Gαi1/3 overexpression enhanced NLGN3-induced signaling. In glioma cells, NLGN3-induced cell growth, proliferation and migration were attenuated by Gαi1/3 depletion with shRNA, but facilitated with Gαi1/3 overexpression. Significantly, Gαi1/3 silencing inhibited orthotopic growth of patient-derived glioma xenografts in mouse brain, whereas forced Gαi1/3-overexpression in primary glioma xenografts significantly enhanced growth. The growth of brain-metastatic human lung cancer cells in mouse brain was largely inhibited with Gαi1/3 silencing. It was however expedited with ectopic Gαi1/3 overexpression. In human glioma Gαi3 upregulation was detected, correlating with poor prognosis.Conclusion:
Gαi1/3 mediation of NLGN3-induced signaling is essential for neuronal-driven glioma growth.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Moléculas de Adesão Celular Neuronais
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Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP
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Glioma
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Proteínas de Membrana
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Proteínas do Tecido Nervoso
Limite:
Aged
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Animals
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Theranostics
Ano de publicação:
2021
Tipo de documento:
Article