Related Experiment Video

Updated: Sep 10, 2025

Evaluation of Amino Acid Consumption in Cultured Bone Cells and Isolated Bone Shafts
06:32

Evaluation of Amino Acid Consumption in Cultured Bone Cells and Isolated Bone Shafts

Published on: April 13, 2022

1.8K

The ATF4-glutamine axis: a central node in cancer metabolism, stress adaptation, and therapeutic targeting

Xing Yan1, Changhong Liu2

  • 1The Second Affiliated Hospital of Dalian Medical University Thoracic surgery, DaLian, Liaoning, PR China.

Cell Death Discovery
|August 19, 2025
PubMed

Insights

Activating transcription factor 4 (ATF4) drives cancer cell survival by regulating Glutamine (Gln) metabolism. Targeting the ATF4-Gln axis offers a promising therapeutic strategy for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolic Pathways

Background:

  • Activating transcription factor 4 (ATF4) is a central regulator of tumor metabolic adaptation.
  • ATF4 controls Glutamine (Gln) uptake, utilization, and redox balance during nutrient deprivation and oxidative stress.

Purpose of the Study:

  • To review the role of ATF4 in integrating stress signals to regulate Gln metabolism in cancer.
  • To highlight the ATF4-Gln axis as a potential therapeutic vulnerability.

Main Methods:

  • Literature review of preclinical studies on ATF4 and Gln metabolism in cancer.
  • Analysis of ATF4's role in tumor survival, metabolic reprogramming, and immune evasion.

Main Results:

  • The ATF4-Gln axis is crucial for tumor survival and metabolic adaptation.
  • Preclinical inhibitors targeting this pathway show therapeutic promise.
  • Understanding this axis provides insights into novel cancer therapies.

Conclusions:

  • The ATF4-Gln axis represents a significant vulnerability in cancer metabolism.
  • Targeting ATF4 offers potential for novel therapeutic strategies.
  • Future research should address tumor heterogeneity and plasticity for effective ATF4-centered therapies.

More Related Videos

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells09:51

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

Published on: June 30, 2023

1.0K
Glutamine Flux Imaging Using Genetically Encoded Sensors10:23

Glutamine Flux Imaging Using Genetically Encoded Sensors

Published on: July 31, 2014

9.7K

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...
3.9K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.9K
Hypothalamic-Pituitary Axis01:37

Hypothalamic-Pituitary Axis

The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
61.6K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.8K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.1K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.6K