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./nMethods: Various genetic strategies were utilized to examine the requirement of Gαi1/3 in NLGN3-driven glioma cell growth./nResults: 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./nConclusion: Gαi1/3 mediation of NLGN3-induced signaling is essential for neuronal-driven glioma growth.

中文翻译：

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神经元驱动的神经胶质瘤生长需要 Gαi1 和 Gαi3

Neuroligin-3 (NLGN3) 是促进胶质瘤细胞生长所必需且足够的。将 Gαi1/3 募集到配体激活受体酪氨酸激酶 (RTK) 对于介导致癌信号传导至关重要。/n方法：利用各种遗传策略来检查 Gαi1/3 在 NLGN3 驱动的神经胶质瘤细胞生长中的需求。/ n结果：NLGN3 诱导的 Akt-mTORC1 和 Erk 激活通过降低 Gαi1/3 表达而受到抑制。相比之下，异位 Gαi1/3 过表达增强了 NLGN3 诱导的信号传导。在胶质瘤细胞中，NLGN3 诱导的细胞生长、增殖和迁移因 shRNA 的 Gαi1/3 消耗而减弱，但 Gαi1/3 过表达促进了细胞生长、增殖和迁移。值得注意的是，Gαi1/3 沉默抑制了小鼠脑中患者来源的胶质瘤异种移植物的原位生长，而原发性胶质瘤异种移植物中的强制 Gαi1/3 过表达显着促进了生长。Gαi1/3 沉默在很大程度上抑制了小鼠脑中脑转移人肺癌细胞的生长。然而，异位 Gαi1/3 过表达加速了它。在人类胶质瘤中检测到 Gαi3 上调，与预后不良相关。/n结论：Gαi1/3 介导 NLGN3 诱导的信号传导对于神经元驱动的神经胶质瘤生长至关重要。