ATF family members as therapeutic targets in cancer: From mechanisms to pharmacological interventions
Xueyao Zhang, Zhijia Li, Xiaochun Zhang, Ziyue Yuan, Lan Zhang, Peng Miao
Abstract
The activating transcription factor (ATF)/ cAMP-response element binding protein (CREB) family represents a large group of basic zone leucine zip (bZIP) transcription factors (TFs) with a variety of physiological functions, such as endoplasmic reticulum (ER) stress, amino acid stress, heat stress, oxidative stress, integrated stress response (ISR) and thus inducing cell survival or apoptosis. Interestingly, ATF family has been increasingly implicated in autophagy and ferroptosis in recent years. Thus, the ATF family is important for homeostasis and its dysregulation may promote disease progression including cancer. Current therapeutic approaches to modulate the ATF family include direct modulators, upstream modulators, post-translational modifications (PTMs) modulators. This review summarizes the structural domain and the PTMs feature of the ATF/CREB family and comprehensively explores the molecular regulatory mechanisms. On this basis, their pathways affecting proliferation, metastasis, and drug resistance in various types of cancer cells are sorted out and discussed. We then systematically summarize the status of the therapeutic applications of existing ATF family modulators and finally look forward to the future prospect of clinical applications in the treatment of tumors by modulating the ATF family. • ATFs exert a critical transcriptional role in cellular homeostasis and survival. • We reviewed the key function of ATFs in stress, apoptosis, autophagy and ferroptosis. • Dual role of ATFs in cancer progress and therapy has been described comprehensively. • We focused on reviewing the direct modulators, upstream modulators and PTMs modulators of ATFs.