The landscape of ATF3 in tumors: Metabolism, expression regulation, therapy approach, and open concerns

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Cellular stress response is fundamental to tumor development and therapeutic outcomes.
• Activating transcription factor 3 (ATF3) is a key stress-responsive protein with diverse roles in biological processes.
• ATF3's involvement in tumor metabolism, regulation, and post-translational modifications is increasingly recognized.

Purpose of the Study:

• To review the multifaceted role of ATF3 in tumor metabolism, including amino acid, lipid, and carbohydrate pathways.
• To delineate the regulatory mechanisms governing ATF3 expression and function, encompassing DNA, epigenetic, and post-translational levels.
• To summarize the therapeutic strategies involving ATF3 in cancer treatment and discuss future clinical trial directions.

Main Methods:

• Literature review synthesizing current research on ATF3 in cancer.
• Analysis of ATF3's regulatory mechanisms: DNA regulation, epigenetic modifications, and post-translational modifications (phosphorylation, ubiquitination, SUMOylation, NEDDylation).
• Examination of ATF3's role in various metabolic pathways and its function beyond transcription, including protein modification.

Main Results:

• ATF3 acts as a central regulator in tumor metabolism, influencing amino acid, lipid, and glycometabolism.
• ATF3 function is modulated by complex regulatory networks, including epigenetic changes and post-translational modifications.
• ATF3 can function as a modifier protein, influencing the ubiquitination of other proteins like p53.

Conclusions:

• ATF3 is a critical nexus in cellular stress response and tumor metabolism, offering potential therapeutic targets.
• A comprehensive understanding of ATF3 regulation and function is essential for developing novel cancer interventions.
• Further research and clinical trials are needed to fully elucidate ATF3's therapeutic potential in oncology.