Work

Activation of cGAS ‐ STING Pathway by DAI ‐Triggered Ferroptosis in CRC Cells Reprograms TAMs Balance to Promote Anti‐Tumor Immunity

Year: 2025

Type: article

Abstract: DNA-dependent activator of interferon-regulatory factors (DAI) has recently been identified to trigger ferroptosis in endothelial cells. However, it remains unclear whether it can also elicit ferroptosis in tumor cells and further remodel the tumor immune microenvironment (TIME). In this study, we found that activation of DAI could also trigger mouse colorectal cancer (CRC) cells ferroptosis. Further experiments showed that DAI-driven ferroptosis induced mitochondria oxidative stress and dysfunction, leading to the release of mitochondrial DNA (mtDNA) into the cytoplasm, which subsequently activated the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway and thereby reprogrammed the TIME by promoting tumor-associated macrophages (TAMs) M1 polarization while preventing TAMs from polarizing towards M2 type, exerting an effective anti-tumor effect, which significantly reduced tumor size and weight. In summary, our findings confirmed DAI-triggered ferroptosis-induced mtDNA-mediated cGAS-STING anti-tumor immunity pathway in mouse CRC cells, providing novel insights into the development of more effective tumor immunotherapeutic strategies that are based on DAI-mediated programmed cell death (PCD).

Source: Cancer Science

DOI: 10.1111/cas.70196

Authors: Pengrui Cheng, Que Yang, Xiao Zhang, Qiang Wang, Bingzheng Zhong

Institutions: Guangzhou First People's Hospital, South China University of Technology, Guangzhou Medical University, Sun Yat-sen University, Sun Yat-sen Memorial Hospital

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,600