Alterations of ubiquitin ligases in human cancer and their association with the natural history of the tumor

S. Confalonieri, M. Quarto, G. Goisis, P. Nuciforo, M. Donzelli, G. Jodice, G. Pelosi, G. Viale, S. Pece, P. P. Di Fiore

Research output: Contribution to journalArticle

Abstract

Protein ubiquitination is critical for many cellular processes, through its ability to regulate protein degradation and various signaling mechanisms. In the ubiquitin (Ub) system, substrate specificity is achieved through the E3 family of Ub ligases. Because alterations of the ubiquitination machinery have been reported in human cancers, the selective interference with Ub ligases might represent a powerful therapeutic tool. Here, we report the first wide survey of misregulation of Ub ligases in cancer. We analysed 82 Ub ligases in nine types of cancer by in situ hybridization on tissue microarrays. We found 27 instances in which an Ub ligase was altered in a given type of tumor, when compared with normal tissues: 21 cases of overexpression and 6 cases of underexpression. We further analysed selected Ub ligases in large cohorts of breast and non-small-cell lung carcinomas. In five, of six, of these extended analyses (HUWE1, CCNB1IP1, SIAH1 and SIAH2 in breast cancer and CCNB1IP1 in lung cancer), we found that the levels of Ub ligases correlated significantly with relevant prognostic factors, and with clinical outcome. Our findings show that the alteration of Ub ligases is a frequent event in cancer and identify candidate targets for molecular therapies.

Original languageEnglish
Pages (from-to)2959-2968
Number of pages10
JournalOncogene
Volume28
Issue number33
DOIs
Publication statusPublished - Aug 20 2009

Keywords

  • Cancer
  • In situ hybridization
  • Tissue microarrays
  • Ubiquitin
  • Ubiquitin E3 ligase

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Fingerprint Dive into the research topics of 'Alterations of ubiquitin ligases in human cancer and their association with the natural history of the tumor'. Together they form a unique fingerprint.

  • Cite this