Neuronal-driven glioma growth requires Gαi1 and Gαi3
| Autor: | Kai-Wen Cheng, Yuan-yuan Liu, Gang Chen, Fang Liu, Yin Wang, Min-Bin Chen, Zhi-qing Zhang, Ya Peng, Li-na Qi, Ke-ran Li, Cong Cao |
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| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
Cell Adhesion Molecules Neuronal Primary Cell Culture Medicine (miscellaneous) Nerve Tissue Proteins Neuron-glioma communication Glioma cell GTP-Binding Protein alpha Subunits Gi-Go Mechanistic Target of Rapamycin Complex 1 Receptor tyrosine kinase Small hairpin RNA Mice Phosphatidylinositol 3-Kinases Downregulation and upregulation Glioma Cell Line Tumor medicine Gene silencing Animals Humans NLGN3 Phosphorylation Pharmacology Toxicology and Pharmaceutics (miscellaneous) Aged Cell Proliferation Neurons biology Cell growth Brain Neoplasms Plant Extracts Membrane Proteins Receptor Protein-Tyrosine Kinases Middle Aged Gαi1/3 medicine.disease Signaling Cancer research biology.protein Female Proto-Oncogene Proteins c-akt Signal Transduction Research Paper |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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