2. Academic Validation
  3. Glucose Deprivation-Induced Disulfidptosis via the SLC7A11-INF2 Axis: Pan-Cancer Prognostic Exploration and Therapeutic Validation

Glucose Deprivation-Induced Disulfidptosis via the SLC7A11-INF2 Axis: Pan-Cancer Prognostic Exploration and Therapeutic Validation

  • Adv Sci (Weinh). 2025 Jul 25:e08556. doi: 10.1002/advs.202408556.
Zhenyu Song 1,  Qiuming Yao 2 3,  Lina Huang 4 5,  Dan Cui 1,  Jun Xie 6,  Leilei Wu 7,  Jianfeng Huang 8,  Bo Zhai 1,  Dan Liu 9,  Xiao Xu 6
Affiliations

Affiliations

  • 1 Mini-invasive Interventional Therapy Center, Shanghai East Hospital, Tongji University, 200120, Shanghai, China.
  • 2 Department of General Practice, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 3 Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, 200032, China.
  • 4 Department of Rehabilitation Medicine, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, China.
  • 5 Key Laboratory of Research and Development on Clinical Molecular Diagnosis for High-Incidence Diseases of Baise, Baise, Guangxi, 533000, China.
  • 6 Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 7 Department of Radiation Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
  • 8 Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 9 GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, 511436, China.
PMID: 40709550 DOI: 10.1002/advs.202408556
Abstract

Disulfidptosis, a novel form of regulated cell death, involves cytoskeletal collapse due to excessive disulfide bond formation, linking metabolism and Reactive Oxygen Species to potential Cancer therapy targets. Recent multi-omics studies highlight the prognostic value of disulfidptosis-related gene (DRG) signatures in pan-cancers; however, the molecular mechanisms underlying their biological functions and therapeutic relevance remain poorly defined. Herein, a DRG score model is constructed using LASSO COX regression across 33 Cancer types, and a nomogram incorporating the DRG score is developed for prognostic prediction. The tumor microenvironment, mutation profiles, and immunotherapy responses are analyzed. The DRG score serves as an independent prognostic factor across cancers, correlating with poor outcomes and malignant features. Glucose deprivation induces Disulfidptosis in SLC7A11high cells (high SLC7A11 expression), especially in cancers with a high DRG score, such as ovarian Cancer. Silencing INF2 prevents Disulfidptosis and decreases susceptibility to irofulven, which can be reversed by GLUT inhibitors. SLC7A11 knockdown reduces Disulfidptosis, restores ATP/NADPH levels, and protects the Cytoskeleton under glucose deprivation, whereas INF2 knockdown impairs cell migration. Moreover, the DRG scores predict prognosis and therapeutic responses. The SLC7A11-INF2 axis regulates Disulfidptosis, migration, and drug sensitivity, highlighting its potential as a marker of metabolic vulnerability in ovarian Cancer.

Keywords

INF2; SLC7A11; disulfidptosis; ovarian cancer; pan‐cancer analysis; prognosis.

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