The isopeptidase USP2a protects human prostate cancer from apoptosis

Carmen Priolo, Dan Tang, Mohan Brahamandan, Barbara Benassi, Ewa Sicinska, Shuji Ogino, Antonella Farsetti, Alessandro Porrello, Stephen Finn, Johann Zimmermann, Phillip Febbo, Massinio Loda

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Abstract

Deubiquitinating enzymes can prevent the destruction of protein substrates prior to proteasomal degradation. The ubiquitin-specific protease 2a (USP2a) deubiquitinates the antiapoptotic proteins Fatty Acid Synthase and Mdm2. Here, we show that when USP2a is overexpressed in nontransformed cells, it exhibits oncogenic behavior both in vitro and in vivo and prevents apoptosis induced by chemotherapeutic agents. Notably, USP2a silencing in several human cancer cell lines results in apoptosis. Gene set enrichment analysis, which focuses on groups of genes sharing biological function or regulatory pathways, was done on microarray expression data from human prostate cancers. The cell death-related gene set, as well as a selected cluster of validated p53 target genes, were significantly enriched in the low USP2a expression group of tumors. Conversely, genes implicated in fatty acid metabolism were significantly associated with tumors expressing high USP2a (44%). The expression profile analysis is consistent with the effects of USP2a on its known targets, i.e., Fatty Acid Synthase and Mdm2, defining a subset of prostate tumors resistant to apoptosis. USP2a thus represents a therapeutic target in prostate cancer.

Original languageEnglish
Pages (from-to)8625-8632
Number of pages8
JournalCancer Research
Volume66
Issue number17
DOIs
Publication statusPublished - Sep 1 2006

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Priolo, C., Tang, D., Brahamandan, M., Benassi, B., Sicinska, E., Ogino, S., Farsetti, A., Porrello, A., Finn, S., Zimmermann, J., Febbo, P., & Loda, M. (2006). The isopeptidase USP2a protects human prostate cancer from apoptosis. Cancer Research, 66(17), 8625-8632. https://doi.org/10.1158/0008-5472.CAN-06-1374