Ubiquitin specific peptidase 32 acts as an oncogene in epithelial ovarian cancer by deubiquitylating farnesyl-diphosphate farnesyltransferase 1

Aya Nakae, Michiko Kodama, Toru Okamoto, Makoto Tokunaga, Hiroko Shimura, Kae Hashimoto, Kenjiro Sawada, Takahiro Kodama, Neal G. Copeland, Nancy A. Jenkins, Tadashi Kimura

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Epithelial ovarian cancer (EOC) is the seventh most common cancer worldwide and the deadliest gynecological malignancy because of its aggressiveness and high recurrence rate. To discover new therapeutic targets for EOC, we combined public EOC microarray datasets with our previous in vivo shRNA screening dataset. The top-ranked gene ubiquitin specific peptidase 32 (USP32), coding a deubiquitinating enzyme, is a component of the ubiquitin proteasome system. Clinically, USP32 is expressed in primary ovarian cancer, especially in metastatic peritoneal tumors, and negatively impacts the survival outcome. USP32 regulates proliferative and epithelial mesenchymal transition capacities that are associated with EOC progression. Proteomic analysis identified farnesyl-diphosphate farnesyltransferase 1 (FDFT1) as a novel substrate of USP32 that is an enzyme in the mevalonate pathway, essentially associated with cell proliferation and stemness. USP32 and FDFT1 expression was higher in tumor spheres than in adherent cells. Inhibition of USP32, FDFT1, or mevalonate pathway considerably suppressed tumor sphere formation, which was restored by adding squalene, a downstream product of FDFT1. These findings suggested that USP32-FDFT1 axis contributes to EOC progression, and could be novel therapeutic targets for EOC treatment.

Original languageEnglish (US)
Pages (from-to)120-127
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume552
DOIs
StatePublished - May 7 2021

Keywords

  • Epithelial ovarian cancer
  • Farnesyl-diphosphate farnesyltransferase 1
  • Mevalonate pathway
  • Ubiquitin specific peptidase 32

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Ubiquitin specific peptidase 32 acts as an oncogene in epithelial ovarian cancer by deubiquitylating farnesyl-diphosphate farnesyltransferase 1'. Together they form a unique fingerprint.

Cite this