{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC7A11, commonly known as xCT, is a critical cystine/glutamate antiporter that imports extracellular cystine in exchange for intracellular glutamate, thereby furnishing cysteine for glutathione biosynthesis and maintaining redox homeostasis. This transport function underlies its dual role in cancer biology: on one hand, its overexpression equips tumor cells with robust antioxidant defenses that protect against oxidative stress and ferroptosis, ultimately promoting tumor growth and survival; on the other hand, the metabolic reprogramming imposed by high SLC7A11 activity creates dependencies on nutrients such as glucose and glutamine, exposing potential therapeutic vulnerabilities."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n \nDisruptions in SLC7A11 activity reverberate beyond redox regulation; in tumor types including gliomas, triple‐negative breast cancers, and non‐small cell lung cancers, altered SLC7A11 levels affect not only intracellular glutathione content but also extracellular glutamate release. Such modulation influences tumor microenvironmental properties—contributing to excitotoxicity, epileptiform seizures, and metabolic stress—and sensitizes cancer cells to ferroptotic inducers and nutrient withdrawal. Moreover, microRNAs targeting SLC7A11, as well as stress response factors like ATF4 and eIF2α phosphorylation, have been shown to regulate its expression and impact apoptosis and oxidative cell death in both malignant and neuronal contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "16"}]}, {"type": "t", "text": "\n \nAt the regulatory level, SLC7A11 is subject to multiple layers of control by oncogenic and stress‐responsive signaling networks. Proteasome inhibition, activation of mTORC2 signaling, mutant p53 sequestration of NRF2, and even ARF interactions can modulate its transcriptional and posttranscriptional stability. Furthermore, epigenetic modifications, microRNA-mediated suppression, and interactions with receptor tyrosine kinases such as EGFR fine-tune its cell surface expression, collectively dictating sensitivity to chemotherapeutic agents, radiotherapy, and ferroptosis inducers. These insights have illuminated SLC7A11 as a promising therapeutic target in diverse malignancies—including bladder, pancreatic, hepatocellular, and glioblastoma—as well as in noncancerous disorders like neurodegeneration and schizophrenia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pranavi Koppula, Li Zhuang, Boyi Gan "}, {"type": "b", "children": [{"type": "t", "text": "Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13238-020-00789-5"}], "href": "https://doi.org/10.1007/s13238-020-00789-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33000412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33000412"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Pranavi Koppula, Yilei Zhang, Li Zhuang, et al. 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