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Protected from the inside: Endogenous histone deacetylase inhibitors and the road to cancer

期刊

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbcan.2011.01.002

关键词

HDACs; HDAC inhibitors; Cancer; HIC1; DBC1; Chfr; RENKCTD11

资金

  1. Associazione Italiana per la Ricerca sul Cancro
  2. Telethon Grant [GGP07118]
  3. Ministry of University and Research
  4. Ministry of Health
  5. Mariani Foundation Italian Institute of Technology
  6. Cenci-Bolognetti Foundation

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Histone deacetylases (HDACs) play a crucial role in several physiological and pathological cell functions, including cell development and cancer, by deacetylating both histones and others proteins. HDACs belong to a large family of enzymes including Class I, II and IV as well as Class III or sirtuins subfamilies, that undergo a complex transcriptional and post-translational regulation. In current years, antitumor therapy is attempting to exploit several chemical classes of inhibitors that target HDACs, frequently reported to be misregulated in cancer. Nevertheless, the identity of gene products directly involved in tumorigenesis and preventing HDAC misregulation in cancer is still poorly understood. Recent evidence has demonstrated that the tumor suppressors HIC1 and DBC1 induce direct repression of Sirt1 function, whereas Chfr and RENKCTD11/KAsH family downregulate HDAC1, by inducing its ubiquitin-dependent degradation. Loss of these gene products leads to imbalanced enhancement of HDAC activity and subsequently to oncogenesis. All these genes are frequently deleted or silenced in human cancers, highlighting the role of endogenous HDAC inhibitors to counteracts HDAC-mediated tumorigenesis. Thus, endogenous HDAC inhibitors represent a promising class of antitumor agents thanks to which oncogenic addiction pathways may be selectively therapeutically targeted. (C) 2011 Elsevier B.V. All rights reserved.

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