SLC7A11-Mediated Disulfidptosis and SPP1+ Cancer-Associated Fibroblasts in Ovarian Cancer Microenvironment Remodeling
10.3971/j.issn.1000-8578.2026.25.0918
- VernacularTitle:SLC7A11介导的双硫死亡与SPP1+癌症相关成纤维细胞在卵巢癌微环境重塑中的作用
- Author:
Shuwei LI
1
;
Yao XIONG
2
;
Yuanzhen ZHANG
1
;
Hua WANG
3
Author Information
1. Center for Reproductive Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China;Clinical Medicine Research Center of Prenatal Diagnosis and Birth Health in Hubei Province, Wuhan 430071, China;Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan 430071, China.
2. Center for Reproductive Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China;Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan 430071, China.
3. Gynecological Oncology Department, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
- Publication Type:BASICRESEARCH
- Keywords:
Disulfidptosis;
SLC7A11;
Ovarian cancer;
Cancer-associated fibroblast;
SPP1;
Single-cell transcriptomics
- From:
Cancer Research on Prevention and Treatment
2026;53(10):782-792
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of SLC7A11-mediated disulfidptosis in regulating the functional heterogeneity of cancer-associated fibroblasts (CAFs) and remodeling the immune microenvironment in ovarian cancer (OC). Methods Utilizing an integrative multi-omics framework, we synchronized transcriptomic data from TCGA and GEO with high-resolution single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. We employed CellChat interactome algorithms to map disulfidptosis-related gene expression profiles across various cellular hierarchies. The mechanistic link between SLC7A11 and SPP1 was further examined via qPCR assays under glucose-deprived, disulfidptosis-inducing conditions. Results SLC7A11 was identified as a crucial regulator of disulfidptosis, exhibiting significant overexpression in OC tissues. Elevated SLC7A11 levels were positively correlated with advanced FIGO stages, increased tumor burden, and resistance to immune checkpoint blockade. scRNA-seq profiling identified a distinct CAF lineage (CAF1/CAF5) characterized by a robust disulfidptosis signature. This subpopulation was associated with epithelial-mesenchymal transition and an immunosuppressive niche via the SPP1-CD44 signaling axis. In situ spatial mapping suggested the localized amplification of SPP1-mediated signaling at the CAF-tumor cell interface, forming high-intensity interactomes with ITGAV, ITGB1, and CD44. Metabolic stress induced by glucose starvation significantly altered the transcriptional profiles of SLC7A11 and SPP1. Notably, the glucose starvation-induced upregulation of NRF2 mRNA in fibroblasts was effectively mitigated by NRF2 knockdown or treatment with the disulfidptosis inhibitor 2-mercaptoethanol. Conclusion SLC7A11-mediated disulfidptosis may activates a subset of CAFs, which may contribute to remodeling the tumor microenvironment and suppressing anti-tumor immunity through the secretion of SPP1.
