Table 3 The roles and mechanism of lipid metabolism in RCC.
From: The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma
Target | Molecular mechanism | Biological function | Reference |
|---|---|---|---|
Annexin A3 (AnxA3) | Isoform switching (reduced 36-kDa/33-kDa ratio) dysregulates vesicular trafficking, promoting lipid droplet (LD) biogenesis. | Drives adipocyte-like phenotype with LD accumulation; grade-dependent lipid dependency (high-grade: FAO; low-grade: de novo lipogenesis). | |
MUC1 | Overexpression upregulates FASN and LDL receptors, amplifying lipid synthesis and storage. | Coordinates Warburg metabolism and cisplatin resistance; soluble MUC1 (CA15-3) correlates with poor progression-free survival. | |
TRIM21 | Degrades SREBF1 to suppress lipogenic enzymes (e.g., FASN, ACC). | Inhibits de novo lipogenesis; synergizes with FAO suppression for metabolic targeting. | [104] |
Chemerin | Inhibits FAO via GPR1/CMKLR1 receptors, sustaining HIF-2α activation. | Maintains pseudohypoxic signaling; promotes lipid storage and tumor survival. | [104] |
HIF-2α/PLIN2 | HIF-2α-driven PLIN2 overexpression stabilizes LDs and protects against ER stress. | Enhances lipid storage and tumor resilience; HIF-2α suppression induces ER stress-mediated death. | [105] |
CPT1A | Downregulation impairs mitochondrial FAO, exacerbating lipid accumulation. | Creates vulnerability to FAO reactivation therapies (e.g., etomoxir). | [106] |
AMPK-GATA3-ECHS1 axis | ECHS1 deficiency triggers fatty acid and BCAA accumulation, activating AMPK-mTORC1 signaling. | Drives proliferation via metabolic crosstalk; links lipid metabolism to growth signaling. | [107] |
MLYCD | Restoration depletes malonyl-CoA, disrupting lipid homeostasis. | Induces ferroptosis; synergizes with mitochondrial-targeted therapies. | [108] |
