ldn-57444 and Ovarian-Neoplasms

High-grade serous ovarian cancer (HGSOC) is characterized by chromosomal instability, DNA damage, oxidative stress, and high metabolic demand that exacerbate misfolded, unfolded, and damaged protein burden resulting in increased proteotoxicity. However, the underlying mechanisms that maintain protein homeostasis to promote HGSOC growth remain poorly understood. This study reports that the neuronal deubiquitinating enzyme, ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), is overexpressed in HGSOC and maintains protein homeostasis. UCHL1 expression was markedly increased in HGSOC patient tumors and serous tubal intraepithelial carcinoma (HGSOC precursor lesions). High UCHL1 levels correlated with higher tumor grade and poor patient survival. UCHL1 inhibition reduced HGSOC cell proliferation and invasion, as well as significantly decreased the

Topics: Animals; Cell Line, Tumor; Cystadenocarcinoma, Serous; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Indoles; Kaplan-Meier Estimate; Mice, Nude; Neoplasm Grading; Ovarian Neoplasms; Oximes; Peptide Hydrolases; Proteasome Endopeptidase Complex; Proteostasis; Ubiquitin Thiolesterase; Xenograft Model Antitumor Assays