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.

Cell Death Discovery
|September 30, 2024
PubMed

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.

Related Concept Videos

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
3.9K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
11.9K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
6.8K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K