Redox–Amino Acid Metabolic Crosstalk in Ovarian Cancer Stem Cells: Integrating Metabolic Reprogramming, Signaling, and the Tumor Microenvironment

作者：Dan Liu, Hua-Wei Yi, Cunjian Yi · 发表于：Antioxidants · 年份：2025 · DOI：10.3390/antiox14121413 · 被引用次数：3 · 研究领域：Cancer, Hypoxia, and Metabolism、Ferroptosis and cancer prognosis、Cancer Research and Treatments

Ovarian cancer stem cells (OCSCs) possess stemness; differentiation capacity; and tolerance to oxidative, metabolic, and therapeutic stress, driving recurrence and chemoresistance. Emerging evidence highlights a synergistic interplay between redox homeostasis and amino acid metabolism in maintaining stemness and treatment resistance. This review integrates redox regulation, amino acid metabolic reprogramming, and tumor microenvironment (TME) signals into a unified "redox-amino acid-TME" framework. OCSCs balance signal transduction and antioxidant defense by fine-tuning reactive oxygen species (ROS) levels. Glutamine, serine/glycine, and sulfur amino acid metabolism collectively generate NADPH and glutathione, sustaining the GPX4/TRX antioxidant systems and suppressing ferroptosis. Branched-chain amino acid (BCAA)-mTOR and tryptophan (Trp)-aryl hydrocarbon receptor (AhR) axes couple amino acid sensing to redox signaling, stabilizing the stem-like phenotype. Under TME stress, including hypoxia, acidity, and nutrient competition, exosomes and stromal components reinforce stemness and immune evasion through metabolic and redox crosstalk. Therapeutically, targeting glutamine metabolism (ASCT2/GLS), serine biosynthesis (PHGDH/SHMT), or antioxidant defenses (xCT/GPX4) disrupts reducing power, increases oxidative stress, and enhances the efficacy of chemotherapy, PARP inhibition, and immunotherapy. Biomarkers such as xCT/GPX4 expression, PHGDH levels, Nrf2 activity, and GSH/NADPH rat...