# Metabolic Messengers: Extracellular Vesicles as Central Mediators of Metabolic Reprogramming in Renal Cell Cancer **Authors:** Qingshu Meng, Liqun Huang, Zhiguo Chen, Rui Lin, Xiaohui Zhou, Guosheng Yang PMC · DOI: 10.3390/biomedicines14020282 · Biomedicines · 2026-01-27 ## TL;DR This review explores how extracellular vesicles mediate metabolic changes in kidney cancer, influencing tumor growth and treatment resistance. ## Contribution The paper highlights the novel role of extracellular vesicles in reprogramming metabolism in renal cell cancer. ## Key findings - Extracellular vesicles transfer metabolic signals between cancer cells and their environment. - EVs contribute to tumor progression by promoting angiogenesis and immune evasion. - Targeting EV-mediated metabolic reprogramming could lead to new therapies for RCC. ## Abstract Renal cell carcinoma (RCC) has been described as a metabolic disease as metabolic alterations are common in disparate RCC etiologies. Extracellular vesicles (EVs), the lipid bilayer-enclosed nanoparticles secreted by all living cells, have emerged as crucial mediators of intercellular and inter-organ communication, capable of shuttling functional proteins, lipids, and nucleic acids between cells. This review summarizes the essential events in tumor-associated metabolic reprogramming with a particular focus on renal cancers. We further explore how EVs released by metabolically deranged cells in cancer with altered cargos reprogram the renal cellular landscape, fostering tumor initiation, proliferation, angiogenesis, immune evasion, and therapy resistance. Understanding this EV-mediated axis not only elucidates the pathophysiological link between these conditions but also helps to unveil novel potential therapeutic targets for RCC patients. ## Linked entities - **Diseases:** renal cell carcinoma (MONDO:0005086), RCC (MONDO:0005086) ## Full-text entities - **Genes:** CMKLR2 (chemerin chemokine-like receptor 2) [NCBI Gene 2825] {aka GPR1}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, MIR193B (microRNA 193b) [NCBI Gene 574455] {aka MIRN193B, mir-193b}, GLS (glutaminase) [NCBI Gene 2744] {aka AAD20, CASGID, DEE71, EIEE71, GAC, GAM}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, LINC01614 (long intergenic non-protein coding RNA 1614) [NCBI Gene 105373869] {aka LCAL4}, MIR204 (microRNA 204) [NCBI Gene 406987] {aka MIRN204, RDICC, miRNA204, mir-204}, Btrc (beta-transducin repeat containing protein) [NCBI Gene 12234] {aka Beta-Trcp1, E3RS-IkappaB, E3RSIkappaB, FWD1, Fbw1a, HOS}, ALDOA (aldolase, fructose-bisphosphate A) [NCBI Gene 226] {aka ALDA, GSD12, HEL-S-87p}, Mettl3 (methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit) [NCBI Gene 56335] {aka 2310024F18Rik, M6A, Spo8}, MIR549A (microRNA 549a) [NCBI Gene 693132] {aka MIR549, MIRN549, hsa-mir-549, hsa-mir-549a, mir-549a}, STING1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 340061] {aka ERIS, MITA, MPYS, NET23, SAVI, STING}, MIR1233-1 (microRNA 1233-1) [NCBI Gene 100302160] {aka MIR1233, MIRN1233, hsa-mir-1233, hsa-mir-1233-1}, EPAS1 (endothelial PAS domain protein 1) [NCBI Gene 2034] {aka ECYT4, HIF2A, HLF, MOP2, PASD2, bHLHe73}, PANK3 (pantothenate kinase 3) [NCBI Gene 79646], H6PD (hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase) [NCBI Gene 9563] {aka CORTRD1, G6PDH, GDH, H6PDH}, CXCR6 (C-X-C motif chemokine receptor 6) [NCBI Gene 10663] {aka BONZO, CD186, CDw186, STRL33, TYMSTR}, HK2 (hexokinase 2) [NCBI Gene 3099] {aka HKII, HXK2}, TRIM62 (tripartite motif containing 62) [NCBI Gene 55223] {aka DEAR1}, SLC2A2 (solute carrier family 2 member 2) [NCBI Gene 6514] {aka GLUT2}, PBRM1 (polybromo 1) [NCBI Gene 55193] {aka BAF180, PB1, RCC, SMARCH1}, ACLY (ATP citrate lyase) [NCBI Gene 47] {aka ACL, ATPCL, CLATP}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, SLC1A5 (solute carrier family 1 member 5) [NCBI Gene 6510] {aka AAAT, ASCT2, ATBO, M7V1, M7VS1, R16}, SLC16A1 (solute carrier family 16 member 1) [NCBI Gene 6566] {aka HHF7, MCT, MCT1, MCT1D}, ISCU (iron-sulfur cluster assembly enzyme) [NCBI Gene 23479] {aka 2310020H20Rik, HML, ISU2, NIFU, NIFUN, hnifU}, EPHA2 (EPH receptor A2) [NCBI Gene 1969] {aka ARCC2, CTPA, CTPP1, CTRCT6, ECK}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, SNHG12 (small nucleolar RNA host gene 12) [NCBI Gene 85028] {aka ASLNC04080, C1orf79, LINC00100, LINC001000, NCRNA00100, PNAS-123}, MIR378A (microRNA 378a) [NCBI Gene 494327] {aka MIR378, MIRN378, hsa-mir-378, hsa-mir-378a, miRNA378}, SLC27A3 (solute carrier family 27 member 3) [NCBI Gene 11000] {aka ACSVL3, FATP3, VLCS-3}, SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513] {aka CSE, DYT17, DYT18, DYT9, EIG12, GLUT}, FKBP5 (FKBP prolyl isomerase 5) [NCBI Gene 2289] {aka AIG6, FKBP51, FKBP54, P54, PPIase, Ptg-10}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, Slc7a5 (solute carrier family 7 (cationic amino acid transporter, y+ system), member 5) [NCBI Gene 20539] {aka 4F2LC, D0H16S474E, Gm42049, LAT1, TA1}, MIR210 (microRNA 210) [NCBI Gene 406992] {aka MIRN210, mir-210}, MIR148B (microRNA 148b) [NCBI Gene 442892] {aka MIRN148B, mir-148b}, SMPD2 (sphingomyelin phosphodiesterase 2) [NCBI Gene 6610] {aka ISC1, NSMASE, NSMASE1}, KAT2B (lysine acetyltransferase 2B) [NCBI Gene 8850] {aka CAF, P/CAF, PCAF}, MIR215 (microRNA 215) [NCBI Gene 406997] {aka MIRN215, miRNA215, mir-215}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, MIR381 (microRNA 381) [NCBI Gene 494330] {aka MIRN381, hsa-mir-381, mir-381}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, Npepps (aminopeptidase puromycin sensitive) [NCBI Gene 19155] {aka AAP-S, MP100, Psa, goku}, SPHK1 (sphingosine kinase 1) [NCBI Gene 8877] {aka SPHK}, CMKLR1 (chemerin chemokine-like receptor 1) [NCBI Gene 1240] {aka CHEMERINR, ChemR23, DEZ, ERV1, RVER1}, SCD (stearoyl-CoA desaturase) [NCBI Gene 6319] {aka FADS5, MSTP008, SCD1, SCDOS, hSCD1}, SLC7A5 (solute carrier family 7 member 5) [NCBI Gene 8140] {aka 4F2LC, CD98, D16S469E, E16, LAT1, MPE16}, RPL17 (ribosomal protein L17) [NCBI Gene 6139] {aka DBA22, L17, PD-1, RPL23, uL22}, RAB22A (RAB22A, member RAS oncogene family) [NCBI Gene 57403], ZNF251 (zinc finger protein 251) [NCBI Gene 90987], Slc1a5 (solute carrier family 1 (neutral amino acid transporter), member 5) [NCBI Gene 20514] {aka AAAT, ASCT2, ATBO, M7V1, M7VS1, R16}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, HDAC5 (histone deacetylase 5) [NCBI Gene 10014] {aka HD5, NY-CO-9}, STX17 (syntaxin 17) [NCBI Gene 55014], KDM1A (lysine demethylase 1A) [NCBI Gene 23028] {aka AIMAH3, AOF2, BHC110, CPRF, KDM1, LSD1}, SLC1A2 (solute carrier family 1 member 2) [NCBI Gene 6506] {aka DEE41, EAAT2, EIEE41, GLT-1, GLT1, HBGT}, TSC2 (TSC complex subunit 2) [NCBI Gene 7249] {aka LAM, PPP1R160, TSC4}, PKM (pyruvate kinase M1/2) [NCBI Gene 5315] {aka CTHBP, HEL-S-30, OIP3, PK3, PKM2, TCB}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1} - **Diseases:** Renal cancer (MESH:D007680), HCC (MESH:D006528), Metabolic Disease (MESH:D008659), Hypoxia (MESH:D000860), Renal cell carcinoma (MESH:D002292), NSCLC (MESH:D002289), Bladder cancer (MESH:D001749), head and neck squamous cell carcinoma (MESH:D000077195), cognitive impairment (MESH:D003072), Hypoxic (MESH:D002534), Breast cancer (MESH:D001943), lung adenocarcinoma (MESH:D000077192), obesity (MESH:D009765), gastric cancer (MESH:D013274), ovarian cancer (MESH:D010051), oncogenesis (MESH:D063646), pulmonary fibrosis (MESH:D011658), aggression (MESH:D010554), Cancer (MESH:D009369), lung cancer (MESH:D008175), insulin resistance (MESH:D007333), bone lesions (MESH:D001847), hyperglycemia (MESH:D006943), brain metastasis (MESH:D009362), thrombosis (MESH:D013927), Melanoma (MESH:D008545), glioma (MESH:D005910), PCa (MESH:D011471), urological cancer (MESH:D014571), inflammatory (MESH:D007249), osteosarcoma (MESH:D012516), injury to (MESH:D014947), pancreatic cancer (MESH:D010190), CRC (MESH:D015179), deficient (MESH:D007153), death (MESH:D003643), tumorigenic (MESH:D002471) - **Chemicals:** arsenic (MESH:D001151), indoleacetate (MESH:C030737), glutamate (MESH:D018698), diacylglycerol (MESH:D004075), TRP (MESH:D014364), citrulline (MESH:D002956), KN (MESH:D007737), MLN4924 (MESH:C539933), oleate (MESH:D019301), sphingolipids (MESH:D013107), STF-31 (MESH:C000599307), nivolumab (MESH:D000077594), branched-chain amino acid (MESH:D000597), ROS (MESH:D017382), quinolinate (MESH:D017378), CB-839 (MESH:C000593334), Ceramide (MESH:D002518), asparagine (MESH:D001216), cholesterol (MESH:D002784), nitric oxide (MESH:D009569), serotonin (MESH:D012701), Glucose (MESH:D005947), Glutamine (MESH:D005973), glutathione (MESH:D005978), citrate (MESH:D019343), sunitinib (MESH:D000077210), phospholipids (MESH:D010743), ATP (MESH:D000255), polyamine (MESH:D011073), sterols (MESH:D013261), prostaglandin E2 (MESH:D015232), Lipid (MESH:D008055), acetyl-CoA (MESH:D000105), free fatty acids (MESH:D005230), Amino Acid (MESH:D000596), glycosphingolipids (MESH:D006028), urea (MESH:D014508), NADPH (MESH:D009249), PEG20 (MESH:C000595209), lactate (MESH:D019344), aspartate (MESH:D001224), FA (MESH:D005227), Arginine (MESH:D001120), phosphatidylcholine (MESH:D010713), monounsaturated FAs (MESH:D005229), carbons (MESH:D002244), dapagliflozin (MESH:C529054), phosphatidylserine (MESH:D010718), tricarboxylic acid (MESH:D014233), creatine (MESH:D003401), pazopanib (MESH:C516667), ketoconazole (MESH:D007654), cholesterol ester (MESH:D002788), serine (MESH:D012694), 2-DG (MESH:D003847), triglycerides (MESH:D014280), sphingomyelin (MESH:D013109), proline (MESH:D011392), pyruvate (MESH:D019289), Cargo (-) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606] - **Mutations:** glutamine to glutamate ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12937659/full.md ## Figures 2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12937659/full.md ## References 174 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937659/full.md --- Source: https://tomesphere.com/paper/PMC12937659