ArticleCell death & disease2023
Super-enhancer-driven MLX mediates redox balance maintenance via SLC7A11 in osteosarcoma.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 24 citations in OpenAlex.
- KIAA1429 knockdown alleviates osteosarcoma progression by destabilizing SLC7A11 mRNA via m6A methylation to promote ferroptosis.International journal of oncology · 2026Article
- From cell to disease: Regulatory networks and mechanisms of super‑enhancers in aging (Review).Molecular medicine reports · 2026Review
- Natural products mediate ferroptosis and immune microenvironment-linked sensitization in osteosarcoma: from chemotherapy resistance to combined therapeutic transformation.Molecular diversity · 2026Review
- Reprogramming lipid metabolism in pediatric cancers.Oncogenesis · 2026Review
- Ferroptosis and metastasis: molecular checkpoints, microenvironmental dynamics, and therapeutic opportunities.Molecular cancer · 2026Review
- Integration of Single-cell Sequencing Analysis Reveals Disulfidptosis Related Molecular Subtype and Novel Prognosis System for Osteosarcoma.Current medicinal chemistry · 2026Article
- [Glutamine metabolic reprogramming in regulating the occurrence and development of osteosarcoma].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Exploring Emerging Therapeutic Targets in Osteosarcoma by Revisiting the Immune and Cancer-Intrinsic Hallmarks of Cancer.Cancers · 2025Review
- Non-coding RNAs-regulated SLC7A11 modulates ferroptosis: a new strategy for cancer therapy.Functional & integrative genomics · 2025Review
- LncDARS-AS1 Regulates ATP1A1 Stability and Enhances NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SLC7A11 is a potential therapeutic target and prognostic biomarker correlated with immune cell infiltration in cervical cancer.Discover oncology · 2025Article
- Specific Knockdown of the NDUFS4 Gene Reveals Important Roles of Ferroptosis in UVB-induced Photoaging.Inflammation · 2025Article
- Targeting super-enhancers in liver cancer: from pathogenic mechanisms to clinical applications.Frontiers in pharmacology · 2025Review
- Osteosarcoma immunometabolism: emerging mechanisms and clinical implications.Frontiers in immunology · 2025Review
- Exploration of the role and mechanism of Rhizoma Paridis total saponins in osteosarcoma based on SPI1/LCN2-mediated ferroptosis.Frontiers in oncology · 2025Article
- Integration of multi-omics data revealed the orphan CpG islands and enhancer-dominatediScience · 2024Article
- Targeting NAT10 inhibits osteosarcoma progression via ATF4/ASNS-mediated asparagine biosynthesis.Cell reports. Medicine · 2024Article
- Whole-exome sequencing identifies protein-coding variants associated with brain iron in 29,828 individuals.Nature communications · 2024Article
- Lipid Peroxidation-Related Redox Signaling in Osteosarcoma.International journal of molecular sciences · 2024Review
- Correlation analysis of disulfidptosis-related gene signatures with clinical prognosis and immunotherapy response in sarcoma.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS) is a common type of bone tumor for which there has been limited therapeutic progress over the past three decades. The prevalence of transcriptional addiction in cancer cells emphasizes the biological significance and clinical relevance of super-enhancers. In this study, we found that Max-like protein X (MLX), a member of the Myc-MLX network, is driven by super-enhancers. Upregulation of MLX predicts a poor prognosis in osteosarcoma. Knockdown of MLX impairs growth and metastasis of osteosarcoma in vivo and in vitro. Transcriptomic sequencing has revealed that MLX is involved in various metabolic pathways (e.g., lipid metabolism) and can induce metabolic reprogramming. Furthermore, knockdown of MLX results in disturbed transport and storage of ferrous iron, leading to an increase in the level of cellular ferrous iron and subsequent induction of ferroptosis. Mechanistically, MLX regulates the glutamate/cystine antiporter SLC7A11 to promote extracellular cysteine uptake required for the biosynthesis of the essential antioxidant GSH, thereby detoxifying reactive oxygen species (ROS) and maintaining the redox balance of osteosarcoma cells. Importantly, sulfasalazine, an FDA-approved anti-inflammatory drug, can inhibit SLC7A11, disrupt redox balance, and induce massive ferroptosis, leading to impaired tumor growth in vivo. Taken together, this study reveals a novel mechanism in which super-enhancer-driven MLX positively regulates SLC7A11 to meet the alleviated demand for cystine and maintain the redox balance, highlighting the feasibility and clinical promise of targeting SLC7A11 in osteosarcoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.