Table 1 The roles and mechanism of glucose metabolism in RCC.
From: The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma
Target | Molecular mechanism | Biological function | Reference |
|---|---|---|---|
HIF-2α/PDK-PDH axis | HIF-2α stabilization activates PDK, phosphorylates and inactivates PDH, diverting pyruvate to lactate production. | Redirects glucose metabolism from mitochondrial oxidation to aerobic glycolysis (Warburg effect). | [90] |
FBP1 | Epigenetic silencing by PRC2 (EZH2-mediated promoter hypermethylation) disrupts FBP1-PRC2 feedback loop. | Reinforces glycolytic dependency; loss of FBP1 promotes tumorigenesis. | [92] |
G6PDH | Upregulation in low-grade ccRCC channels glucose-6-phosphate into the pentose phosphate pathway (PPP). | Supports NADPH production (antioxidant defense) and ribose-5-phosphate synthesis (nucleotide biosynthesis). | |
UQCRH | Downregulated via promoter hypermethylation, exacerbating mitochondrial dysfunction. | Sustains Warburg metabolism; rescuing UQCRH restores oxidative phosphorylation. | [93] |
circFOXP1/miR-423-5p | circFOXP1 sponges miR-423-5p to upregulate U2AF2. | Amplifies glycolytic flux, promoting tumor proliferation and invasion. | [94] |
DEPDC1 | Activates HIF1α via AKT/mTOR signaling under hypoxia. | Sustains glycolysis and confers resistance to tyrosine kinase inhibitors (TKIs). | [95] |
3-Bromopyruvate (3BrPA) | Selectively depletes ATP in ccRCC cells with mitochondrial defects. | Induces apoptosis in glycolytic-dependent tumors; ineffective in oxidative or FH-mutant tumors. | [96] |
Lactate/Pyruvate ratio | Elevated in ccRCC patient urine, normalizes post-tumor resection. | Biomarker of glycolytic activity and tumor burden. | [91] |
