Disulfidptosis in tumor progression

Abstract Disulfidptosis, a regulated cell death modality driven by the cystine transporter solute carrier family 7 member 11 (SLC7A11), is characterized by actin cytoskeleton collapse under glucose starvation. This review systematically elucidates the pivotal role of disulfidptosis in tumor metaboli...

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Main Authors: Senlin Wan, Changming Liang, Chengwei Wu, Song Wang, Jiawei Wang, Lishuai Xu, Xu Zhang, Yinfen Hou, Yabin Xia, Li Xu, Xiaoxu Huang
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02495-9
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author Senlin Wan
Changming Liang
Chengwei Wu
Song Wang
Jiawei Wang
Lishuai Xu
Xu Zhang
Yinfen Hou
Yabin Xia
Li Xu
Xiaoxu Huang
author_facet Senlin Wan
Changming Liang
Chengwei Wu
Song Wang
Jiawei Wang
Lishuai Xu
Xu Zhang
Yinfen Hou
Yabin Xia
Li Xu
Xiaoxu Huang
author_sort Senlin Wan
collection DOAJ
description Abstract Disulfidptosis, a regulated cell death modality driven by the cystine transporter solute carrier family 7 member 11 (SLC7A11), is characterized by actin cytoskeleton collapse under glucose starvation. This review systematically elucidates the pivotal role of disulfidptosis in tumor metabolic reprogramming, with a focus on its molecular mechanisms and distinctions from other cell death pathways. The core mechanisms include SLC7A11-mediated cystine overload and NRF2/c-Myc-regulated pentose phosphate pathway activation. By integrating multiomics data and single-cell transcriptomics, we comprehensively decipher the heterogeneous expression patterns of disulfidptosis-related genes (DRGs) and their dynamic interplay with immune microenvironment remodeling. Furthermore, the coexpression networks of DRGs and disulfidptosis-related long noncoding RNAs (DRLs) offer novel insights into tumor diagnosis, prognosis, and targeted therapy. Therapeutically, SLC7A11 inhibitors (e.g., HG106) and glucose transporter inhibitors (e.g., BAY-876) demonstrate efficacy by exploiting metabolic vulnerabilities, whereas natural compounds synergizing with immune checkpoint blockade provide strategies to counteract immunosuppressive microenvironments. Through interdisciplinary collaboration and clinical translation, disulfidptosis research holds transformative potential in redefining precision oncology.
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spelling doaj-art-c11cd442589f4ffeae1fbbb72e3f1c012025-08-20T03:52:19ZengNature Publishing GroupCell Death Discovery2058-77162025-04-0111111610.1038/s41420-025-02495-9Disulfidptosis in tumor progressionSenlin Wan0Changming Liang1Chengwei Wu2Song Wang3Jiawei Wang4Lishuai Xu5Xu Zhang6Yinfen Hou7Yabin Xia8Li Xu9Xiaoxu Huang10Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical CollegeDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical CollegeDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical CollegeDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical CollegeDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical CollegeDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical CollegeDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical CollegeDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical CollegeDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical CollegeDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical CollegeDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical CollegeAbstract Disulfidptosis, a regulated cell death modality driven by the cystine transporter solute carrier family 7 member 11 (SLC7A11), is characterized by actin cytoskeleton collapse under glucose starvation. This review systematically elucidates the pivotal role of disulfidptosis in tumor metabolic reprogramming, with a focus on its molecular mechanisms and distinctions from other cell death pathways. The core mechanisms include SLC7A11-mediated cystine overload and NRF2/c-Myc-regulated pentose phosphate pathway activation. By integrating multiomics data and single-cell transcriptomics, we comprehensively decipher the heterogeneous expression patterns of disulfidptosis-related genes (DRGs) and their dynamic interplay with immune microenvironment remodeling. Furthermore, the coexpression networks of DRGs and disulfidptosis-related long noncoding RNAs (DRLs) offer novel insights into tumor diagnosis, prognosis, and targeted therapy. Therapeutically, SLC7A11 inhibitors (e.g., HG106) and glucose transporter inhibitors (e.g., BAY-876) demonstrate efficacy by exploiting metabolic vulnerabilities, whereas natural compounds synergizing with immune checkpoint blockade provide strategies to counteract immunosuppressive microenvironments. Through interdisciplinary collaboration and clinical translation, disulfidptosis research holds transformative potential in redefining precision oncology.https://doi.org/10.1038/s41420-025-02495-9
spellingShingle Senlin Wan
Changming Liang
Chengwei Wu
Song Wang
Jiawei Wang
Lishuai Xu
Xu Zhang
Yinfen Hou
Yabin Xia
Li Xu
Xiaoxu Huang
Disulfidptosis in tumor progression
Cell Death Discovery
title Disulfidptosis in tumor progression
title_full Disulfidptosis in tumor progression
title_fullStr Disulfidptosis in tumor progression
title_full_unstemmed Disulfidptosis in tumor progression
title_short Disulfidptosis in tumor progression
title_sort disulfidptosis in tumor progression
url https://doi.org/10.1038/s41420-025-02495-9
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