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The critical role of Gαi3 in oral squamous cell carcinoma cell growth
Quan Li1, Zhiyue Huang2, Zihan Li2
1Department of Stomatology, The Second Affiliated Hospital of Soochow University, Suzhou, China. liquan232@163.com.
Abstract:
The identification of novel and effective therapeutic targets for oral squamous cell carcinoma (OSCC) is of paramount importance. This study investigates the expression, potential functions, and mechanistic insights of G protein inhibitory subunit 3 (Gαi3) in OSCC. Gαi3 is found to be upregulated in human OSCC tissues as well as in various primary and established OSCC cells. In different OSCC cells, silencing of Gαi3 through shRNA resulted in inhibited cell proliferation and migration, while also inducing apoptosis. Knockout (KO) of Gαi3 via the CRISPR/Cas9 method produced significant anti-cancer effects in OSCC cells. Conversely, ectopic overexpression of Gαi3 enhanced OSCC cell growth, promoting cell proliferation and migration. Gαi3 plays a crucial role in activating the Akt-mTOR signaling pathway in OSCC cells. Silencing or KO of Gαi3 led to decreased phosphorylation levels of Akt and S6K, whereas overexpression of Gαi3 increased their phosphorylation. Restoration of Akt-mTOR activation through a constitutively active mutant Akt1 mitigated the anti-OSCC effects induced by Gαi3 shRNA. In vivo, Gαi3 silencing significantly suppressed the growth of subcutaneous OSCC xenografts in nude mice, concomitant with inactivation of the Akt-mTOR pathway and induction of apoptosis. Collectively, these findings underscore the critical role of Gαi3 in OSCC cell growth both in vitro and in vivo.
Insights
G protein inhibitory subunit 3 (Gαi3) is upregulated in oral squamous cell carcinoma (OSCC), driving tumor growth. Inhibiting Gαi3 suppressed OSCC progression and induced apoptosis, highlighting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Oral squamous cell carcinoma (OSCC) requires novel therapeutic targets for effective treatment.
- G protein inhibitory subunit 3 (Gαi3) is implicated in various cellular processes.
- Understanding Gαi3's role in OSCC is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the expression, function, and mechanism of G protein inhibitory subunit 3 (Gαi3) in oral squamous cell carcinoma (OSCC).
- To evaluate Gαi3 as a potential therapeutic target for OSCC treatment.
Main Methods:
- Gαi3 expression analysis in OSCC tissues and cells.
- Gαi3 knockdown using shRNA and knockout using CRISPR/Cas9 in OSCC cells.
- Gαi3 overexpression studies in OSCC cells.
- Western blot analysis to assess Akt-mTOR pathway activation.
- In vivo studies using subcutaneous OSCC xenografts in nude mice.
Main Results:
- Gαi3 was significantly upregulated in OSCC tissues and cells.
- Gαi3 silencing or knockout inhibited OSCC cell proliferation, migration, and induced apoptosis.
- Gαi3 overexpression promoted OSCC cell growth, proliferation, and migration.
- Gαi3 activates the Akt-mTOR signaling pathway in OSCC.
- Gαi3 silencing suppressed tumor growth in vivo and inactivated the Akt-mTOR pathway.
Conclusions:
- G protein inhibitory subunit 3 (Gαi3) is a critical driver of OSCC progression.
- Gαi3 promotes OSCC growth by activating the Akt-mTOR signaling pathway.
- Gαi3 represents a promising therapeutic target for oral squamous cell carcinoma.
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