SLC7A11: the Achilles heel of tumor?

The non-natriuretic-dependent glutamate/cystine inverse transporter-system Xc- is composed of two protein subunits, SLC7A11 and SLC3A2, with SLC7A11 serving as the primary functional component responsible for cystine uptake and glutathione biosynthesis. SLC7A11 is implicated in tumor development through its regulation of redox homeostasis, amino acid metabolism, modulation of immune function, and induction of programmed cell death, among other processes relevant to tumorigenesis. In this paper, we summarize the structure and biological functions of SLC7A11, and discuss its potential role in tumor therapy, which provides a new direction for precision and personalized treatment of tumors.

• Publication year

  2024

• Venue

  Frontiers in Immunology

• Publication date

  2024-07-08

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fimmu.2024.1438807PMID 39040097PMCID 11260620
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Targeted activation of ferroptosis in colorectal cancer via LGR4 targeting overcomes acquired drug resistance

  2024cited by this paper
• Exploring the mystery of tumor metabolism: Warburg effect and mitochondrial metabolism fighting side by side.

  2024cited by this paper
• Correction to “Curcumin induces ferroptosis in non‐small‐cell lung cancer via activating autophagy”

  2024cited by this paper
• Ferroptosis: a new hunter of hepatocellular carcinoma

  2024cited by this paper
• Integrated multiomic analysis reveals disulfidptosis subtypes in glioblastoma: implications for immunotherapy, targeted therapy, and chemotherapy

  2024cited by this paper
• Disulfidptosis: Six Riddles Necessitating Solutions

  2024cited by this paper
• SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells

  2023cited by this paper
• Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axis

  2023influential reference
• Disulfidptosis: a new target for metabolic cancer therapy

  2023cited by this paper
• Ginsenoside Rh3 induces pyroptosis and ferroptosis through the Stat3/p53/NRF2 axis in colorectal cancer cells

  2023cited by this paper
• Vitamin D Promotes Ferroptosis in Colorectal Cancer Stem Cells via SLC7A11 Downregulation

  2023cited by this paper
• Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis

  2023cited by this paper
• Silencing lncRNA HCG18 regulates GPX4-inhibited ferroptosis by adsorbing miR-450b-5p to avert sorafenib resistance in hepatocellular carcinoma

  2023cited by this paper
• The amino acid transporter SLC7A11 expression in breast cancer

  2023cited by this paper
• Disulfidptosis: Disulfide Stress Mediates a Novel Cell Death Pathway via Actin Cytoskeletal Vulnerability

  2023cited by this paper
• Marine Alkaloid Lepadins E and H Induce Ferroptosis for Cancer Chemotherapy.

  2023cited by this paper
• Disulfidptosis: a new form of programmed cell death

  2023cited by this paper
• Saikosaponin A triggers cell ferroptosis in hepatocellular carcinoma by inducing endoplasmic reticulum stress-stimulated ATF3 expression.

  2023influential reference
• The role of ROS in tumour development and progression

  2022cited by this paper
• Macrophage-specific xCT deficiency drives immune activation and boosts responses to immune checkpoint blockade in lung cancer.

  2022cited by this paper
• Targeted xCT‐mediated Ferroptosis and Protumoral Polarization of Macrophages Is Effective against HCC and Enhances the Efficacy of the Anti‐PD‐1/L1 Response

  2022cited by this paper
• Hypoxia Enhances Glioma Resistance to Sulfasalazine-Induced Ferroptosis by Upregulating SLC7A11 via PI3K/AKT/HIF-1α Axis

  2022cited by this paper
• Vitamin K: A new guardian against ferroptosis.

  2022cited by this paper
• Repression of the antiporter SLC7A11/Glutathione/Glutathione Peroxidase 4 axis drives ferroptosis of vascular smooth muscle cells to facilitate vascular calcification.

  2022cited by this paper
• SOCS2-enhanced ubiquitination of SLC7A11 promotes ferroptosis and radiosensitization in hepatocellular carcinoma

  2022cited by this paper
• Comprehensive analysis of ferroptosis-related gene signatures as a potential therapeutic target for acute myeloid leukemia: A bioinformatics analysis and experimental verification

  2022cited by this paper
• Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications.

  2022cited by this paper
• The Role of SLC7A11 in Cancer: Friend or Foe?

  2022cited by this paper
• Ursolic acid enhances the antitumor effects of sorafenib associated with Mcl-1-related apoptosis and SLC7A11-dependent ferroptosis in human cancer.

  2022cited by this paper
• Active Compounds in Zingiber officinale as Possible Redox Inhibitors of 5-Lipoxygenase Using an In Silico Approach

  2022cited by this paper
• Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer

  2022cited by this paper
• Agrimonolide inhibits cancer progression and induces ferroptosis and apoptosis by targeting SCD1 in ovarian cancer cells.

  2022influential reference
• SLC7A11, a Potential Therapeutic Target Through Induced Ferroptosis in Colon Adenocarcinoma

  2022cited by this paper
• Macropinocytosis is an alternative pathway of cysteine acquisition and mitigates sorafenib-induced ferroptosis in hepatocellular carcinoma

  2022cited by this paper
• Pan-Cancer Analyses Confirmed the Ferroptosis-Related Gene SLC7A11 as a Prognostic Biomarker for Cancer

  2022cited by this paper
• Hallmarks of Cancer: New Dimensions.

  2022cited by this paper
• Intra-Tumoral Expression of SLC7A11 Is Associated with Immune Microenvironment, Drug Resistance, and Prognosis in Cancers: A Pan-Cancer Analysis

  2021cited by this paper
• The Harmonious Interplay of Amino Acid and Monocarboxylate Transporters Induces the Robustness of Cancer Cells

  2021cited by this paper
• Ursolic Acid Regulates Cell Cycle and Proliferation in Colon Adenocarcinoma by Suppressing Cyclin B1

  2021cited by this paper
• Cellular degradation systems in ferroptosis

  2021cited by this paper
• System Xc−: a key regulatory target of ferroptosis in cancer

  2021cited by this paper
• Broadening horizons: the role of ferroptosis in cancer

  2021cited by this paper
• Curcumin induces ferroptosis in non‐small‐cell lung cancer via activating autophagy

  2021cited by this paper
• Bioactivity of natural biflavonoids in metabolism-related disease and cancer therapies.

  2021cited by this paper
• Inhibition of xCT Suppresses the Efficacy of Anti-PD-1/-L1 Melanoma Treatment through Exosomal PD-L1 Induced Macrophage M2 Polarization.

  2021cited by this paper
• Targeting SLC1A5 and SLC3A2/SLC7A5 as a Potential Strategy to Strengthen Anti-Tumor Immunity in the Tumor Microenvironment

  2021cited by this paper
• Signals of pseudo-starvation unveil the amino acid transporter SLC7A11 as key determinant in the control of Treg cell proliferative potential.

  2021cited by this paper
• Amino acid transporters as emerging therapeutic targets in cancer

  2021cited by this paper
• Levobupivacaine Induces Ferroptosis by miR-489-3p/SLC7A11 Signaling in Gastric Cancer

  2021cited by this paper
• Tirapazamine suppress osteosarcoma cells in part through SLC7A11 mediated ferroptosis.

  2021cited by this paper
• IL‐1β‐Induced Elevation of Solute Carrier Family 7 Member 11 Promotes Hepatocellular Carcinoma Metastasis Through Up‐regulating Programmed Death Ligand 1 and Colony‐Stimulating Factor 1

  2021cited by this paper
• Abrogation of HnRNP L enhances anti-PD-1 therapy efficacy via diminishing PD-L1 and promoting CD8+ T cell-mediated ferroptosis in castration-resistant prostate cancer

  2021cited by this paper
• Glutamine Metabolism Regulators Associated with Cancer Development and the Tumor Microenvironment: A Pan-Cancer Multi-Omics Analysis

  2021cited by this paper
• Tanshinone IIA inhibits gastric cancer cell stemness through inducing ferroptosis

  2021cited by this paper
• The roles of ferroptosis regulatory gene SLC7A11 in renal cell carcinoma: A multi‐omics study

  2021cited by this paper
• Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy

  2020cited by this paper
• Discovery of a novel ferroptosis inducer-talaroconvolutin A—killing colorectal cancer cells in vitro and in vivo

  2020cited by this paper
• NADPH debt drives redox bankruptcy: SLC7A11/xCT-mediated cystine uptake as a double-edged sword in cellular redox regulation

  2020cited by this paper
• Erastin induces ferroptosis via ferroportin-mediated iron accumulation in endometriosis.

  2020cited by this paper
• MULTIFACETED ROLE OF BRANCHED-CHAIN AMINO ACID METABOLISM IN CANCER

  2020cited by this paper
• Ferroptosis: machinery and regulation

  2020cited by this paper
• The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects

  2020cited by this paper
• Emerging Mechanisms and Disease Relevance of Ferroptosis.

  2020cited by this paper
• Combinative treatment of β-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation

  2020cited by this paper
• The Chemistry and Biology of Ferroptosis.

  2020cited by this paper
• Cysteine depletion induces pancreatic tumor ferroptosis in mice

  2020cited by this paper
• Ferroptosis, a novel pharmacological mechanism of anti-cancer drugs.

  2020cited by this paper
• Correction to: ROS and diseases: role in metabolism and energy supply

  2020cited by this paper
• The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma

  2020cited by this paper
• Ferroptosis, a new form of cell death: opportunities and challenges in cancer

  2019cited by this paper
• CD8+ T cells regulate tumor ferroptosis during cancer immunotherapy

  2019cited by this paper
• Molecular mechanisms of ferroptosis and its role in cancer therapy

  2019cited by this paper
• Suppression of the SLC7A11/glutathione axis causes synthetic lethality in KRAS-mutant lung adenocarcinoma.

  2019cited by this paper
• ROS and diseases: role in metabolism and energy supply

  2019cited by this paper
• Dysregulation of glutamate transport enhances Treg function that promotes VEGF blockade resistance in glioblastoma.

  2019cited by this paper
• Imidazole Ketone Erastin Induces Ferroptosis and Slows Tumor Growth in a Mouse Lymphoma Model.

  2019cited by this paper
• Sigma‐1 receptor protects against ferroptosis in hepatocellular carcinoma cells

  2019cited by this paper
• Glutaminolysis‐related genes determine sensitivity to xCT‐targeted therapy in head and neck squamous cell carcinoma

  2019cited by this paper
• 5-Lipoxygenase as a drug target: A review on trends in inhibitors structural design, SAR and mechanism based approach.

  2019cited by this paper
• SLC3A2/CD98hc, autophagy and tumor radioresistance: a link confirmed

  2019cited by this paper
• Pseudolaric acid B triggers ferroptosis in glioma cells via activation of Nox4 and inhibition of xCT.

  2018cited by this paper
• Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer

  2018cited by this paper
• Vitamin E and its anticancer effects

  2018cited by this paper
• ROS-modulated therapeutic approaches in cancer treatment

  2017cited by this paper
• Activation of the p62‐Keap1‐NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells

  2016cited by this paper
• Metallothionein‐1G facilitates sorafenib resistance through inhibition of ferroptosis

  2016cited by this paper
• Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element*

  2015cited by this paper
• The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells.

  2015cited by this paper
• Regulation of ferroptotic cancer cell death by GPX4.

  2014cited by this paper
• Pharmacological inhibition of cystine–glutamate exchange induces endoplasmic reticulum stress and ferroptosis

  2014cited by this paper
• The SLC3 and SLC7 families of amino acid transporters.

  2013cited by this paper
• Hallmarks of cancer: the next generation.

  2011cited by this paper
• Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells.

  2008cited by this paper
• ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis

  2007cited by this paper
• Glutamate Inhibits Chondral Mineralization through Apoptotic Cell Death Mediated by Retrograde Operation of the Cystine/Glutamate Antiporter*

  2006cited by this paper
• Cystine Deprivation Induces Oligodendroglial Death: Rescue by Free Radical Scavengers and by a Diffusible Glial Factor

  1996cited by this paper
• Hepatocellular carcinoma.

  1986cited by this paper

• The Achilles’ heel of hepatocellular carcinoma: ginsenoside compound K as a novel GPX4 degrader promotes ferroptosis in hepatocellular carcinoma

  2026cites this paper
• Sodium Butyrate Alleviates IBD by Modulating SIRT1-Involved Ferroptosis and Inhibition of Macrophage Ferroptosis.

  2026cites this paper
• Inhibition of IRE1α kinase increases ferroptosis resistance in triple-negative breast cancer cells.

  2026cites this paper
• Inducing Ferroptosis: Sensitization Strategy for Radiotherapy and Its Application.

  2026cites this paper
• Disulfidptosis-based cancer therapy: Opportunity and challenge

  2026cites this paper
• Amino Acid Metabolic Reprogramming in Clear Cell Renal Cell Carcinoma: Pathogenic Mechanisms and Therapeutic Targeting.

  2026cites this paper
• Cancer Neuroscience: Linking Neuronal Plasticity with Brain Tumor Growth and Resistance

  2026cites this paper
• A multifunctional nanocatalytic ferroptosis amplifier based on glutathione scavenging and lipid peroxidation amplification for cancer therapy.

  2026cites this paper
• The mist of ferroptosis: The Orpheus journey of mitochondria - Exploring the symphony of cell fate.

  2025cites this paper
• Exploring the Mechanisms of the Ferroptosis-Related Gene TGFBR1 in Autoimmune Uveitis Based on Machine Learning Models

  2025cites this paper
• Ferroptosis in neurodegenerative diseases: potential mechanisms of exercise intervention

  2025cites this paper
• Ferroptosis in ocular diseases: mechanisms, crosstalk with other cell death pathways, and therapeutic prospects

  2025influential citation
• Histone methyltransferase G9a drives ferroptosis to aggravate vascular calcification by inhibiting SLC7A11 transcription.

  2025cites this paper
• LncRNA SLC7A11AR promotes lung adenocarcinoma progression by inhibiting ferroptosis via promoting SLC7A11 expression

  2025cites this paper
• KNOP1 interacts with NMNAT1 to govern ferroptosis and tumor growth in breast cancer via regulating FoxO1-dependent GPX4 transcription.

  2025cites this paper
• ACSL4 at the helm of the lipid peroxidation ship: a deep-sea exploration towards ferroptosis

  2025influential citation
• Quinazolinone derivatives as potential anti-tumor agents: Structural features and molecular mechanisms in inducing cell death (Review)

  2025cites this paper
• Clinical Practice and Prognostic Molecular Biomarkers in Clear Cell Renal Cell Carcinoma: Latest Advancements

  2025cites this paper
• Disulfidptosis mechanisms and therapeutic implications in cancer metabolic reprogramming and future perspectives

  2025influential citation
• Identification of TRIM59 as a Key Biomarker for Ferroptosis Resistance and Immunotherapy Response in Bladder Cancer via Multi-Omics Integration and Machine Learning.

  2025cites this paper
• Ferroptosis for food safety: An innovative and sustainable strategy in pathogenic bacteria inactivation and antimicrobial resistance modulation.

  2025cites this paper
• Exploiting metabolic cell death for cancer therapy

  2025cites this paper
• FAP-targeted radionuclide therapy induces ferroptosis in cancer-associated fibroblasts via disrupting iron homeostasis and redox balance

  2025cites this paper
• The dual role of SLC7A11 in tumor drug resistance: mechanisms, challenges, and therapeutic potential.

  2025cites this paper
• Selenoproteins: Minute yet vital players governing cellular fate

  2025cites this paper
• Non-coding RNAs-regulated SLC7A11 modulates ferroptosis: a new strategy for cancer therapy

  2025cites this paper
• SLC7A11 as a molecular nexus of prognosis, resistance, and therapeutic roadmap in cancer: A systematic review and meta-analysis.

  2025cites this paper
• Exploring Emerging Therapeutic Targets in Osteosarcoma by Revisiting the Immune and Cancer-Intrinsic Hallmarks of Cancer

  2025cites this paper
• The Gut Microbiota–Ferroptosis Axis: Emerging Perspectives in Gastrointestinal Tumorigenesis and Progression

  2025cites this paper
• Bibliometric and visual analysis of ferroptosis in cardiovascular diseases

  2025cites this paper
• Ferroptosis-associated RNA-binding proteins predict clinical outcomes in head and neck squamous cell carcinoma

  2025cites this paper
• The potential of natural herbal plants in the treatment and prevention of non-small cell lung cancer: An encounter between ferroptosis and mitophagy.

  2025cites this paper
• The long-term in vitro co-exposure of polyethylene terephthalate (PET) nanoplastics and cigarette smoke condensate exacerbates the induction of carcinogenic traits.

  2025cites this paper
• Secoiridoid-enriched extra virgin olive oil extracts enhance mitochondrial activity and antioxidant response in colorectal cancer cells: The role of Oleacein and Oleocanthal in PPARγ interaction.

  2025cites this paper
• Ferroptosis and renal fibrosis: mechanistic insights and emerging therapeutic targets

  2025cites this paper
• The Development and Assessment of a Unique Disulfidptosis-Associated lncRNA Profile for Immune Microenvironment Prediction and Personalized Therapy in Gastric Adenocarcinoma

  2025cites this paper
• Disulfide bond-related gene signature development for bladder cancer prognosis prediction and immune microenvironment characterization

  2025cites this paper
• SLC7A11-mediated cell death mechanism in cancer: a comparative study of disulfidptosis and ferroptosis

  2025cites this paper
• Formononetin triggers ferroptosis in triple-negative breast cancer cells by regulating the mTORC1/SREBP1/SCD1 pathway

  2024cites this paper
• cDTL contributes to breast cancer progression through regulating redox homeostasis via affecting the function of system xc.

  2024cites this paper
• Decoding ferroptosis: transforming orthopedic disease management

  2024cites this paper
• Intracellular Iron Deficiency and Abnormal Metabolism, Not Ferroptosis, Contributes to Homocysteine-Induced Vascular Endothelial Cell Death

  2024cites this paper