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

Table 2 Reported ubiquitin-specific peptidases inhibitors in breast cancer study

Target		Breast cancer subtype	Experiment	Pathways
USP1	Pimozide	ER negative BC, TNBC	In vitro; In vivo	Cell cycle, AKT signaling pathway, EMT, MMP-9, vimentin, STAT3[76,78,79]
	Trifluoperazin	TNBC	In vitro; In vivo	G0/G1 arrest, cyclinD1/CDK4, cyclinE/CDK2[80]
	Rottlerin	ER positive BC, TNBC, CSCs	In vitro	NFκB, cyclin D-1, p38 MAPK, AMPK, proteasome inhibition, Skp2[81-84]
	ML323	BC	In vitro; In vivo	KPNA2[20]
USP2	6-TG	BRCA2-defective PARP inhibitor-resistant BC, BRCA1-mutant BC, TNBC	In vitro; In vivo	DNA repair, PI3K-AKT, apoptosis pathway, lncRNA-miRNA-mRNA ceRNA network, DNMT1[85,87,88,90]
	ML364	ER-positive BC	In vitro	Endocytic degradation[91]
USP7	Costunolide	metastatic TNBC, BC	In vitro	NF-κB signaling, cell cycle regulation, c-Myc/p53, AKT/14-3-3 pathway, p38MAPK pathways[92-95]
USP7/47	P5091	BC	In vitro	EMT[96]
USP14	b-AP15	ER positive BC, TNBC	In vitro; In vivo	Autophagy, ERα signaling[98,99]
	IU1	AR-positive BC	In vitro; In vivo	Wnt/β-catenin, PI3K/AKT pathways[55]
	Auranofin	ER positive BC, TNBC	In vitro; In vivo	PTGR1 expression, ERK1/2-MYC, p38 MAPK signaling pathway, mitochondrial apoptosis[100-102]
USP9x	WP1130	ER-negative BC	In vitro	Mcl-1[43]

USPs: Ubiquitin-specific peptidases; ER: Estrogen receptor; BC: Breast cancer; TNBC: Triple-negative breast cancer; AKT: Protein kinase B; EMT: Epithelial mesenchymal transition; MMP-9: Matrix metallopeptidase 9; STAT3: Signal transducerand activator of transcription 3; CDK: Cyclin-Dependent Kinase; NFκB: Nuclear factor kappa-B; MAPK: Mitogen-activated protein kinase; AMPK: Adenosine 5'-monophosphate (AMP)-activated protein kinase; Skp2: S-phase kinase-associatedprotein 2; KPNA2: Karyopherinα2; CSCs: Cancer stem cells; BRCA: Breast cancer 1; PARP: Poly (ADP-ribose) polymerase; DNA: Deoxyribonucleic acid; PI3K: Phosphoinositide 3-kinase; AKT: Protein kinase B; lncRNA: Long non-coding RNA; miRNA: MicroRNA; ceRNA: Competing endogenous RNA; DNMT1: DNA (cytosine-5-)-methyltransferase 1; AR: Androgen receptor; MAPK: Mitogen-activated protein kinase; PTGR1: Prostaglandin reductase 1; ERK1/2: Extracellular regulated protein kinases 2; Mcl-1: Myeloid cell leukemia-1.