Related Experiment Video

Updated: Aug 5, 2026

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase
09:51

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase

Published on: June 30, 2023

ATF4 orchestrates cancer hallmarks: Stress adaptation, metabolic reprogramming and immune suppression

Zhiyi Peng1, Tong Xu1, Zhenhua Xia1

  • 1The Second Clinical Medical College, Lanzhou University, Lanzhou, People's Republic of China.

Iscience
|July 28, 2026
PubMed

Insights

Activating transcription factor 4 (ATF4) plays a dual role in cancer by regulating metabolism and immunity. Understanding its switch between tumor promotion and suppression is key for developing targeted cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Stress Response

Background:

  • Activating transcription factor 4 (ATF4) is a key regulator of cellular adaptation to stress.
  • ATF4 exhibits context-dependent roles in cancer, influencing both tumor promotion and suppression.
  • The precise mechanisms governing ATF4's opposing functions and its therapeutic potential remain unclear.

Purpose of the Study:

  • To review the molecular mechanisms by which ATF4 integrates various stress signals.
  • To analyze how ATF4 orchestrates metabolic reprogramming and immune evasion in cancer.
  • To evaluate the therapeutic landscape and challenges of targeting ATF4 in oncology.

Main Methods:

  • Literature review of studies on ATF4 in cancer.
  • Analysis of molecular pathways regulated by ATF4 under stress conditions.
  • Assessment of current and potential therapeutic strategies targeting ATF4.

Main Results:

  • ATF4 integrates endoplasmic reticulum, oxidative, and nutrient deprivation stress signals.
  • ATF4 coordinates metabolic reprogramming and immune evasion in cancer.
  • Targeting ATF4 presents challenges in pharmacological selectivity, toxicity, and druggability.

Conclusions:

  • ATF4 is a critical mediator of cancer cell adaptation and immune modulation.
  • Further research is needed to define ATF4's precise roles and overcome therapeutic hurdles.
  • Harnessing ATF4 as a precision oncology target requires addressing its complexities.
Keywords:
ATF4ISRimmune suppressionintegrated stress responsemetabolic reprogramming

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Related Concept Videos

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,...
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,...
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...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...