Neuronal-driven Glioma Growth Requires Gαi1 and Gαi3

Overview

Journal Theranostics

Date 2021 Aug 10

PMID 34373757

Citations 40

Authors

Yin Wang

Yuan-Yuan Liu

Min-Bin Chen

Kai-Wen Cheng

Li-Na Qi

Zhi-Qing Zhang

Ya Peng

Ke-Ran Li

Fang Liu

Gang Chen

Cong Cao

Affiliations

Soon will be listed here.

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

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