Related Experiment Video

Updated: Jul 18, 2025

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
07:29

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies

Published on: June 20, 2015

19.7K

Metformin promotes cGAS/STING signaling pathway activation by blocking AKT phosphorylation in gastric cancer

Qian Shen1, Lei Yang1, Chengguo Li1

  • 1Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Heliyon
|August 21, 2023
PubMed

Insights

Metformin activates the cGAS/STING pathway in gastric cancer by suppressing SOX2/AKT, offering potential for immunotherapy. This study explores metformin

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • The cyclic GMP-AMP synthase (cGAMP) synthase (cGAS)/stimulator of interferon genes (STING) pathway is crucial for innate immunity and anti-tumor responses.
  • Metformin, an anti-diabetic drug, shows anti-cancer effects, but its role in gastric cancer's cGAS/STING pathway is unexplored.

Purpose of the Study:

  • To investigate the effect of metformin on the cGAS/STING signaling pathway in gastric cancer.
  • To elucidate the molecular mechanisms underlying metformin's action in gastric cancer immunotherapy.

Main Methods:

  • Bioinformatic analysis to assess metformin's correlation with tumor immunity.
  • Experimental validation of metformin's function in activating the cGAS/STING pathway in gastric cancer cell lines.
  • KEGG pathway enrichment analysis and Western blotting to examine the PI3K/AKT pathway and SOX2/AKT interactions.

Main Results:

  • Metformin demonstrated a significant relationship with tumor immunity across multiple cancers.
  • Metformin was confirmed to activate the cGAS/STING signaling pathway in gastric cancer cells.
  • Metformin negatively correlated with the PI3K/AKT pathway, suppressing AKT phosphorylation and SOX2-mediated signaling.

Conclusions:

  • Metformin activates the cGAS/STING pathway in gastric cancer by inhibiting the SOX2/AKT axis.
  • Metformin shows potential as a therapeutic agent for enhancing gastric cancer immunotherapy.
Keywords:
AKTGastric cancerMetforminSOX2cGAS/STING

More Related Videos

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

760
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies07:47

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies

Published on: September 15, 2023

1.5K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.7K
Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
230
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.7K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.4K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K