The role of ATF3 in the crosstalk between cellular stress response and ferroptosis in tumors.

During cellular stress, which results in DNA damage, protein, glucose, and lipid metabolism disorders, and redox homeostasis imbalance, various cellular stress responses are triggered, such as DNA damage response, endoplasmic reticulum stress, integrated stress response, and oxidative stress. These cellular stress responses play an important role in the disease process and have a dual role. Activating transcription factor3 belongs to the ATF/CREB family and is activated by stress. It is a transcription factor that plays an important role in gene regulation. It mainly participates in the regulation of disease progression by regulating metabolic homeostasis. Its expression is related to the prognosis of various tumors. ATF3, which is elevated in tumor cells by stress stimulation, not only participates in the repair of internal environment homeostasis mediated by cellular stress response, but also plays a key role in programmed cell death mediated by cellular stress response. Cellular stress response can affect the occurrence of ferroptosis through multiple pathways, with ATF3 being a key protein. This review first introduces the mechanism of ATF3 expression regulation, then summarizes the dual role of ATF3 in DNA damage response, endoplasmic reticulum stress, integrated stress response, and oxidative stress. Finally, it emphasizes the mechanism of ATF3 affecting ferroptosis through DNA damage response, and ER and oxidative stress. This study comprehensively reviews the role of ATF3 in tumors from multiple perspectives, providing new directions for tumor treatment.