Emerging potential of ubiquitin-specific proteases and ubiquitin-specific proteases inhibitors in breast cancer treatment

Table 1 Ubiquitin-specific proteases studied in breast cancer

USPs	Expression	Potential role in breast cancer	Signal pathway
USP1	Upregulated	Tumor promoter	KPNA2, ERα signaling, Hippo signaling pathway, TGF-β signaling[20-23]
USP4	Upregulated	Tumor suppressor	PDCD4, circBMPR2, PAK5-DNPEP pathway, Relaxin/TGF-β1/Smad2/MMP-9 signaling, TGF-β signaling[24-28]
USP7	Upregulated	Tumor promoter	PHF8,DNA repair, Aurora-A kinase, ECT2[29-34]
USP9X	Upregulated	Tumor promoter, Tumor suppressor	CEP131, Hippo Pathway, Notch signaling, Cyclin D1,Wnt signaling, TRAIL, YAP1[35,37,38,40,41,45,46]
USP11	Upregulated	Tumor promoter	TGFβ signaling, DNA damage, XIAP[47-49]
USP14	Upregulated	Tumor promoter	CyclinB1, Wnt/β-catenin and PI3K/AKT pathways, cell cycle[53,54]
USP15	Upregulated	Tumor promoter	DNA repair, ERα signaling[65,66]
USP18	Upregulated	Tumor promoter	AKT/Skp2 pathway[68]
USP20	Upregulated	Tumor promoter	SNAI2[69]
USP22	Upregulated	Tumor promoter	c-Myc, Hh pathway[57,58]
USP28	Upregulated	Tumor suppressor	HIF-independent pathway, LSD1[71,72]
USP32	Upregulated	Tumor promoter	Unknown[73]
USP33	Upregulated	Tumor suppressor	Slit-Robo signaling[74]
USP37	Upregulated	Tumor promoter	Stemness, epithelial-mesenchymal transition[60]
USP39	Upregulated	Tumor promoter	G0/G1-phase arrest, CHEK2[62,63]

USPs: Ubiquitin-specific peptidases; KPNA2: Karyopherin subunit α-2; ER: Estrogen receptor; TGF-β: Transforming growth factor-β; PDCD4: Programmed cell death 4 protein; circBMPR2: Bone morphogenetic protein 2; PAK5: P21-activated kinase; DNPEP:Aspartyl aminopeptidase; MMP-9: Matrix metallopeptidase 9;Smad2: Small mothers against decapentaplegic 2; PHF8: Plant homeodomain finger protein 8; DNA: Deoxyribonucleic acid; ECT2: Epithelial cell transforming 2; CEP131: Centrosomal protein 131; TRAIL: TNF-related apoptosis-inducing ligand; YAP1: Yes-associated protein 1; XIAP: X-linked inhibitor of apoptosis protein; PI3K: Phosphoinositide 3-kinase; AKT: Protein kinase B; Skp2: S-phase kinase-associatedprotein 2; SNAI2: Snail family transcriptional repressor 2; Hh: Hedgehog; HIF: Hypoxia inducible factor-1; LSD1: Human lysine specific demethylases l; CHEK2: checkpoint kinase 2.