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

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 Cystath...

Full description

Bibliographic Details
Main Authors: Junjia Liu, Xinyi Lu, Siyu Zeng, Rong Fu, Xindong Wang, Lingtao Luo, Ting Huang, Xusheng Deng, Hualei Zheng, Shaoqian Ma, Dan Ning, Lili Zong, Shu-Hai Lin, Yongyou Zhang
Format: Article
Language:English
Published: Elsevier 2024-05-01
Series:Redox Biology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213231724000946
Description
Summary: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 β-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.
ISSN:2213-2317