# Dual Roles of Ubiquitin-Specific Peptidase 10 (USP10) in Cancer **Authors:** Yifei Zhai, Liming Zhou, Manhan Zhao, Qiong Lin PMC · DOI: 10.3390/cells15060518 · 2026-03-13 ## TL;DR This paper reviews how USP10, an enzyme involved in cancer, can both suppress and promote tumor growth depending on the cancer type. ## Contribution The paper highlights the dual functional roles of USP10 in cancer and its potential as a therapeutic target. ## Key findings - USP10 deubiquitinates both tumor suppressor and oncogenic proteins. - Aberrant USP10 expression is linked to multiple cancer types. - USP10 inhibitors may serve as targeted cancer therapies. ## Abstract Ubiquitin-specific peptidase 10 (USP10) deubiquitinates multiple signaling proteins in cancer cells. These USP10 substrates contain both tumor suppressors and oncogenic proteins, thus conferring both inhibitory and promoting effects of USP10 on tumorigenesis and progression. This review focuses on the dual roles of USP10 in various cancer types and addresses the association of aberrant USP10 expression with the development of various types of cancers, including hepatocellular carcinoma, lung cancer, breast cancer, prostate cancer, gastric cancer, and acute and chronic myelogenous leukemia. In addition, this review discusses the potential applications of USP10 inhibitors as targeted drugs for cancer therapy. ## Linked entities - **Genes:** USP10 (ubiquitin specific peptidase 10) [NCBI Gene 9100] - **Diseases:** hepatocellular carcinoma (MONDO:0007256), lung cancer (MONDO:0005138), breast cancer (MONDO:0004989), prostate cancer (MONDO:0005159), gastric cancer (MONDO:0001056) ## Full-text entities - **Genes:** ARL3 (ARF like GTPase 3) [NCBI Gene 403] {aka ARFL3, JBTS35, RP83}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, EIF4G1 (eukaryotic translation initiation factor 4 gamma 1) [NCBI Gene 1981] {aka EIF-4G1, EIF4F, EIF4G, EIF4GI, P220, PARK18}, TNFRSF10B (TNF receptor superfamily member 10b) [NCBI Gene 8795] {aka CD262, DR5, KILLER, KILLER/DR5, TRAIL-R2, TRAILR2}, ATM (ATM serine/threonine kinase) [NCBI Gene 472] {aka AT1, ATA, ATC, ATD, ATDC, ATE}, ZEB1 (zinc finger E-box binding homeobox 1) [NCBI Gene 6935] {aka AREB6, BZP, DELTAEF1, FECD6, NIL2A, PPCD3}, BBC3 (BCL2 binding component 3) [NCBI Gene 27113] {aka JFY-1, JFY1, PUMA}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], ABCG2 (ATP binding cassette subfamily G member 2 (JR blood group)) [NCBI Gene 9429] {aka ABC15, ABCP, BCRP, BMDP, CD338, CDw338}, RAF1 (Raf-1 proto-oncogene, serine/threonine kinase) [NCBI Gene 5894] {aka CMD1NN, CRAF, NS5, Raf-1, c-Raf}, FOXC1 (forkhead box C1) [NCBI Gene 2296] {aka ARA, ASGD3, FKHL7, FREAC-3, FREAC3, IGDA}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, G3BP2 (G3BP stress granule assembly factor 2) [NCBI Gene 9908], PLAGL2 (PLAG1 like zinc finger 2) [NCBI Gene 5326] {aka ZNF900}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, TBX21 (T-box transcription factor 21) [NCBI Gene 30009] {aka IMD88, T-PET, T-bet, TBET, TBLYM}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, NOTCH1 (notch receptor 1) [NCBI Gene 4851] {aka AOS5, AOVD1, TAN1, hN1}, FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322] {aka CD135, FLK-2, FLK2, STK1}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, STK11 (serine/threonine kinase 11) [NCBI Gene 6794] {aka LKB1, PJS, hLKB1}, SIRT6 (sirtuin 6) [NCBI Gene 51548] {aka SIR2L6, hSIRT6}, ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) [NCBI Gene 25] {aka ABL, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, HDAC6 (histone deacetylase 6) [NCBI Gene 10013] {aka CPBHM, HD6, JM21, KDAC6, PPP1R90}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, FOXQ1 (forkhead box Q1) [NCBI Gene 94234] {aka HFH1}, BECN1 (beclin 1) [NCBI Gene 8678] {aka ATG6, VPS30, beclin1}, MDM2 (MDM2 proto-oncogene) [NCBI Gene 4193] {aka ACTFS, HDMX, LSKB, hdm2}, NLRP7 (NLR family pyrin domain containing 7) [NCBI Gene 199713] {aka CLR19.4, HYDM, NALP7, NOD12, OZEMA25, PAN7}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, TSC2 (TSC complex subunit 2) [NCBI Gene 7249] {aka LAM, PPP1R160, TSC4}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, CCN1 (cellular communication network factor 1) [NCBI Gene 3491] {aka CYR61, GIG1, IBP-10, IGFBP-10, IGFBP10}, KLF4 (KLF transcription factor 4) [NCBI Gene 9314] {aka EZF, GKLF}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, CPT1A (carnitine palmitoyltransferase 1A) [NCBI Gene 1374] {aka CPT I, CPT1, CPT1-L, CPTI-L, L-CPT1}, MAP1LC3A (microtubule associated protein 1 light chain 3 alpha) [NCBI Gene 84557] {aka ATG8E, LC3, LC3A, MAP1ALC3, MAP1BLC3}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, USP10 (ubiquitin specific peptidase 10) [NCBI Gene 9100] {aka UBPO}, GDF10 (growth differentiation factor 10) [NCBI Gene 2662] {aka BIP, BMP-3b, BMP3B}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PDGFRB (platelet derived growth factor receptor beta) [NCBI Gene 5159] {aka CD140B, IBGC4, IMF1, JTK12, KOGS, OPDKD}, PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 5563] {aka AMPK, AMPK2, AMPKa2, PRKAA}, PDK1 (pyruvate dehydrogenase kinase 1) [NCBI Gene 5163], STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, AXIN1 (axin 1) [NCBI Gene 8312] {aka AXIN, CMDOH, PPP1R49}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, SMAD4 (SMAD family member 4) [NCBI Gene 4089] {aka DPC4, JIP, MADH4, MYHRS} - **Diseases:** OS (MESH:D012516), carcinogenic (MESH:D011230), steatosis (MESH:D005234), inflammation (MESH:D007249), CML (MESH:D015464), Breast Cancer (MESH:D001943), hypoxic (MESH:D002534), lymph node metastasis (MESH:D008207), renal cell carcinoma (MESH:D002292), hypoxia (MESH:D000860), Cancer (MESH:D009369), thyroid cancer (MESH:D013964), gliomas (MESH:D005910), melanoma (MESH:D008545), metabolic diseases (MESH:D008659), Colorectal Cancer (MESH:D015179), prostate tumor (MESH:D011472), neurodegenerative diseases (MESH:D019636), pancreatic adenocarcinoma (MESH:D010190), NSCLC (MESH:D002289), renal tumor (MESH:D007680), HCC (MESH:D006528), ESCC (MESH:D004938), Gastric Cancer (MESH:D013274), metastasis (MESH:D009362), Prostate Cancer (MESH:D011471), AML (MESH:D015470), Leukemia (MESH:D007938), bone cancer (MESH:D001859), carcinogenesis (MESH:D063646), Lung Cancer (MESH:D008175), Pancreatic Ductal Adenocarcinoma (MESH:D021441), injury to (MESH:D014947) - **Chemicals:** proline (MESH:D011392), glutathione (MESH:D005978), phosphatidylinositol-3,4,5-trisphosphate (MESH:C060974), cystine (MESH:D003553), ROS (MESH:D017382), Adriamycin (MESH:D004317), cisplatin (MESH:D002945), lipid (MESH:D008055), hydroxyproline (MESH:D006909), PIP3 (-), PIP2 (MESH:D019269) - **Species:** Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Homo sapiens (human, species) [taxon 9606] - **Cell lines:** Wu-5 — Homo sapiens (Human), Medulloblastoma, Cancer cell line (CVCL_M136), SKP2 — Homo sapiens (Human), Chronic myelogenous leukemia, BCR-ABL1 positive, Cancer cell line (CVCL_TL40) ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13025103/full.md --- Source: https://tomesphere.com/paper/PMC13025103