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These findings collectively highlight therapeutic potential in targeting Warburg effect regulators through pharmacological or epigenetic approaches, with key glycolytic enzymes (HK2, PKM2, LDHA) representing strategic intervention points to disrupt both metabolic fueling and immunosuppressive mechanisms in CRC [21]

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Although glutamate is the major downstream product of glutamine, glutamate supplementation during glutamine deprivation cannot rescue the impaired cell growth or mitochondrial respiration 16,43,44,45 , indicating that mitochondrial GLS-catalyzed cleavage of the gamma-nitrogen of glutamine is essential for glutaminolysis

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