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The Role of Activating Transcription Factor 3 in Cancer: A Key Regulator of Oncogenesis with Therapeutic Potential
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ELHAM Naderzadeh   , Mohammad Kargar , Ali Farhadi * , Mohammad Javad Mokhtari |
| Shiraz University of Medical Sciences , farhadi_a@sums.ac.ir |
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Abstract: (13 Views) |
Objectives: Cancer is a complex and heterogeneous disease resulting from genetic and epigenetic alterations that disrupt normal cellular processes. Activating transcription factor 3 (ATF3), a member of the ATF/CREB family, plays a context-dependent role in cancer, acting as either an oncogene or a tumor suppressor depending on cellular and tissue-specific conditions. While, ATF3 has been implicated in stress responses, apoptosis, and immune regulation, its precise role in cancer remains controversial. This systematic review aims to comprehensively analyze ATF3’s function across different cancer types, examining its potential as a therapeutic target.
Method: A systematic search of articles in PubMed, ScienceDirect, and Web of Science databases was conducted on March 10, 2025, using the keywords ATF3, activating transcription factor 3, ATF3 protein, cancer, and neoplasm, and ultimately 74 articles were approved and used.
Findings: Our analysis highlights ATF3’s role in regulating key oncogenic and tumor-suppressive pathways in prostate, breast, colon, lung, and liver cancer. ATF3 interacts with multiple signaling networks, including p53, NF-κB, and TGF-β pathways, influencing cell proliferation, apoptosis, metastasis, and chemoresistance. Depending on the tumor microenvironment, ATF3 can either promote or inhibit cancer progression.
Conclusion: ATF3 is a crucial regulator of cellular homeostasis, integrating extracellular and intracellular stress signals into genomic responses. Its dual role in oncogenesis underscores the need for further investigation to determine its context-dependent functions. A better understanding of ATF3’s regulatory mechanisms may provide new insights into targeted therapies aimed at modulating its activity in specific cancer types.
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| Keywords: ATF3, Cancer, Neoplasm, Tumor Suppressor, Systematic Review |
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Type of Study: Review |
Subject:
medicine, paraclinic
Received: 2025/07/16 | Revised: 2025/11/3 | Accepted: 2025/10/26
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