Table 6 The roles and mechanism of other metabolism in RCC.
From: The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma
Target | Molecular mechanism | Metabolic pathway | Biological function | Reference |
|---|---|---|---|---|
TRIM65 | Ubiquitinates and degrades tumor suppressor BTG3, alleviating G2/M cell cycle arrest. | Ubiquitin-proteasome system | Promotes RCC proliferation via metabolic reprogramming. | [126] |
FKBP51 | Promotes autophagic degradation of TIMP3 to enhance tumor invasion and migration. | Autophagy | Drives metastatic progression and aggressiveness in RCC. | [127] |
PAK4 | Targeted by PROTAC drug PpD, which inhibits PAK4 and synergizes with anti-PD-1 therapy. | Kinase signaling | Suppresses tumor proliferation and enhances immunotherapy response. | [128] |
EIF3D | Interacts with GRP78 to stabilize proteins and activate unfolded protein response (UPR). | Protein homeostasis | Induces therapy resistance in sunitinib-resistant RCC. | [129] |
OXPHOS (chRCC) | Reduced mtDNA content impairs ETC complex subunit expression and OXPHOS function. | Mitochondrial respiration | Characterizes chRCC, distinguishes it from benign renal oncocytoma; linked to GSH overproduction. | [130] |
PGC-1α (ccRCC) | Suppressed via HIF/Dec1-dependent mechanism, reducing Tfam and mitochondrial function. | Mitochondrial biogenesis | Promotes Warburg effect; restoring PGC-1α rescues OXPHOS and enhances therapy sensitivity. | [131] |
PFKFB4 | Overexpressed in ccRCC; activates PPP via phosphorylation of NCOA3-FBP1 complex. | Pentose phosphate pathway (PPP) | Drives sunitinib resistance, tumor progression, and redox homeostasis. | [132] |
ABL1 kinase (FH-deficient RCC) | Activated in FH-deficient tumors, enhancing glycolysis and NRF2-mediated antioxidant defenses. | Aerobic glycolysis and oxidative stress | Vandetanib inhibits ABL1, prolonging survival in aggressive FH-deficient RCC. | [133] |
