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Publication : ATF3-CBS signaling axis coordinates ferroptosis and tumorigenesis in colorectal cancer.

First Author  Liu J Year  2024
Journal  Redox Biol Volume  71
Pages  103118 PubMed ID  38490069
Mgi Jnum  J:346386 Mgi Id  MGI:7615664
Doi  10.1016/j.redox.2024.103118 Citation  Liu J, et al. (2024) ATF3-CBS signaling axis coordinates ferroptosis and tumorigenesis in colorectal cancer. Redox Biol 71:103118
abstractText  The induction of ferroptosis is promising for cancer therapy. However, the mechanisms enabling cancer cells to evade ferroptosis, particularly in low-cystine environments, remain elusive. Our study delves into the intricate regulatory mechanisms of Activating transcription factor 3 (ATF3) on Cystathionine beta-synthase (CBS) under cystine deprivation stress, conferring resistance to ferroptosis in colorectal cancer (CRC) cells. Additionally, our findings establish a positively correlation between this signaling axis and CRC progression, suggesting its potential as a therapeutic target. Mechanistically, ATF3 positively regulates CBS to resist ferroptosis under cystine deprivation stress. In contrast, the suppression of CBS sensitizes CRC cells to ferroptosis through targeting the mitochondrial tricarboxylic acid (TCA) cycle. Notably, our study highlights that the ATF3-CBS signaling axis enhances ferroptosis-based CRC cancer therapy. Collectively, the findings reveal that the ATF3-CBS signaling axis is the primary feedback pathway in ferroptosis, and blocking this axis could be a potential therapeutic approach for colorectal cancer.
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