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Notably, PC-3M (prostate cancer cell lines) subpopulations with stem-like features exhibit heightened glutamine dependency characterized by elevated GLS1 expression and enhanced reductive carboxylation activity, forming a bidirectional regulatory loop between glutamine metabolism and epigenetic reprogramming (44)

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It is characterized by ROS-induced dissociation of the oxygen-sensitive kinase KEAP1, activating the NRF2 signaling pathway and caspase-8-dependent cell death [241, 242]

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