Work

FGA modulates immune infiltration and tumor progression via SLC7A11/xCT-mediated disulfidptosis in the tumor microenvironment of lung adenocarcinoma

Year: 2025

Type: article

Abstract: Emerging evidence highlights the tumor microenvironment’s (TME) crucial role in driving tumorigenesis and malignant progression. Disulfidptosis has recently been discovered as a non-apoptotic cell death mechanism triggered by intracellular disulfide stress. However, the impact of disulfidptosis within the dynamic modulation of the immune and stromal components in the TME of lung adenocarcinoma (LUAD) remains poorly characterized. In the presented study, RNA-seq and clinical data of LUAD patients were downloaded from TCGA; screening for genes associated with disulfidptosis and immune infiltration, revealed that fibrinogen alpha chain (FGA) modulates immune infiltration via disulfidptosis regulation. We also in-vitro experiments identified FGA suppression abrogates disulfidptosis through SLC7A11/xCT downregulation and attenuated disulfidptosis while concurrently enhancing malignant phenotypes, including cellular proliferation, migratory capacity, and invasive potential in LUAD models. This study reveals that FGA functions as a tumor suppressor that can impede the tumorigenesis of LUAD by modulating xCT expression, suggesting a novel therapeutic strategy enabling modulation of disulfidptosis for LUAD management.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2025.1595900

Authors: Gen Li, Qiuping Li, Sheng Yang, Dongmei Guo, Yanling Tao, Yan Jia

Institutions: Tongji University, Tongji Hospital, Affiliated Hospital of Jining Medical University, Jining Medical University

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: $3,801