Related Experiment Video

Updated: Jul 6, 2025

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells
09:51

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

854

Second messenger 2'3'-cyclic GMP-AMP (2'3'-cGAMP): the cell autonomous and non-autonomous roles in cancer progression

Xiao-Yu Ma1,2,3, Man-Man Chen1,2,3, Ling-Hua Meng4,5,6

  • 1Division of Anti-tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China.

Acta Pharmacologica Sinica
|January 4, 2024
PubMed

Insights

Cytosolic DNA triggers the cGAS-cGAMP-STING pathway, crucial for immunity. This pathway also impacts cancer progression, offering new therapeutic targets for cancer treatment.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Biology

Background:

  • Cytosolic double-stranded DNA (dsDNA) accumulation in cancer cells activates cyclic GMP-AMP synthase (cGAS).
  • cGAS synthesizes 2'3'-cyclic GMP-AMP (2'3'-cGAMP), activating the stimulator of interferon genes (STING) signaling pathway.
  • The cGAS-cGAMP-STING pathway is vital for innate immunity and viral defense, but also implicated in cancer progression.

Purpose of the Study:

  • To review the synthesis, transmission, and degradation of 2'3'-cGAMP.
  • To elucidate the dual functions of 2'3'-cGAMP in cancer progression via STING-dependent mechanisms.
  • To discuss therapeutic strategies targeting the cGAMP-mediated antitumor response.

Main Methods:

  • Literature review of scientific publications on cGAS-cGAMP-STING pathway in cancer.
  • Analysis of cell-autonomous and non-autonomous roles of 2'3'-cGAMP.
  • Exploration of STING signaling modulation in tumor cells and the tumor microenvironment.

Main Results:

  • 2'3'-cGAMP acts as both an intracellular messenger and an extracellular immunotransmitter.
  • Cancer cell-derived 2'3'-cGAMP modulates immune cells in the tumor microenvironment by activating STING.
  • The cGAS-cGAMP-STING pathway exhibits dual roles in cancer, influencing progression and immune response.

Conclusions:

  • 2'3'-cGAMP plays a significant role in cancer progression through both cell-intrinsic and extrinsic pathways.
  • Targeting the cGAS-cGAMP-STING pathway presents a promising avenue for novel cancer therapies.
  • Understanding 2'3'-cGAMP dynamics is crucial for developing effective immunotherapies.
Keywords:
2’3’-cGAMPCDNsENPP1TREX1cGAS-STINGtumor microenvironment

More Related Videos

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

8.9K
RhoC GTPase Activation Assay09:58

RhoC GTPase Activation Assay

Published on: August 22, 2010

12.5K

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
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
46.9K
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...
6.5K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.5K
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