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  • Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) Promotes Uterine Serous Cancer Cell Proliferation and Cell Cycle Progression.

Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) Promotes Uterine Serous Cancer Cell Proliferation and Cell Cycle Progression.

Cancers (2020-01-08)
Suet-Ying Kwan, Chi-Lam Au-Yeung, Tsz-Lun Yeung, Angela Rynne-Vidal, Kwong-Kwok Wong, John I Risinger, Hui-Kuan Lin, Rosemarie E Schmandt, Melinda S Yates, Samuel C Mok, Karen H Lu
ABSTRACT

Uterine serous carcinoma (USC) is the most aggressive form of endometrial cancer, with poor survival rates and high recurrence risk. Therefore, the purpose of this study was to identify therapeutic targets that could aid in the management of USC. By analyzing endometrial cancer samples from The Cancer Genome Atlas (TCGA), we found Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) to be highly expressed in USC and to correlate with poorer overall survival. UCHL1 silencing reduced cell proliferation in vitro and in vivo, cyclin B1 protein levels and cell cycle progression. Further studies showed that UCHL1 interacts with cyclin B1 and increases cyclin B1 protein stability by deubiquitination. Treatment of USC-bearing mice with the UCHL1-specific inhibitor reduced tumor growth and improved overall survival. Our findings suggest that cyclin B1 is a novel target of UCHL1 and targeting UCHL1 is a potential therapeutic strategy for USC.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-UCHL1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Duolink® In Situ Red Starter Kit Mouse/Rabbit
Sigma-Aldrich
L-(−)-Glucose, ≥99%
Sigma-Aldrich
LDN-57444, ≥98% (HPLC)