Table 4 The roles and mechanism of amino acid metabolism in RCC.
From: The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma
Target | Molecular mechanism | Biological function | Reference |
|---|---|---|---|
GLS1 | Long non-coding RNA MIR4435-2HG interacts with STAT1 to transcriptionally activate GLS1, promoting glutamine hydrolysis. | Drives glutamine dependency in FH-deficient RCC; GLS1 inhibition (e.g., CB-839) suppresses tumor growth. | [110] |
JHU-083 | Aminotransferase inhibitor blocking nitrogen flux from glutamine to biosynthetic pathways. | Reduces tumor growth in preclinical models; highlights aminotransferase dependency. | [109] |
IL-23-Treg axis | Glutamate depletion by tumor cells triggers TAM-derived IL-23 secretion, promoting Treg proliferation and suppressing cytotoxic T cells. | Facilitates immune evasion; IL-23 pathway inhibition enhances anti-PD-1 efficacy. | [111] |
HIF-mediated reductive carboxylation (RC) | HIF activation in VHL-deficient RCC induces RC to generate citrate from glutamine-derived α-KG under hypoxia. | Supports tumor survival in hypoxic niches; citrate restoration inhibits RC. | [112] |
MYC | MYC overexpression amplifies glutaminolysis, increasing glutamate availability for biosynthesis. | Drives proliferation in MYC-driven RCC; glutaminase inhibition slows tumor progression. | [113] |
ASS1 | Epigenetic activation of ASS1 in metastatic ccRCC enhances arginine synthesis via the urea cycle. | Supports arginine-dependent tumor growth and metastasis. | [114] |
xCT transporter/GGT1 | ChRCC relies on cystine uptake via xCT to maintain glutathione; GGT1 deficiency impairs glutathione synthesis. | Induces ferroptosis vulnerability; GGT1 overexpression suppresses ChRCC growth. | [115] |
PLCG2/IP3/Ca2+/PKC pathway | Regulates endocytic uptake of amino acids from extracellular macromolecules in nutrient-poor environments. | Sustains ChRCC survival; pathway inhibition disrupts amino acid uptake and tumor adaptation. | [116] |
