TY - JOUR
T1 - Protected from the inside
T2 - Endogenous histone deacetylase inhibitors and the road to cancer
AU - Di Marcotullio, Lucia
AU - Canettieri, Gianluca
AU - Infante, Paola
AU - Greco, Azzura
AU - Gulino, Alberto
PY - 2011/4
Y1 - 2011/4
N2 - 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 REN
KCTD11/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.
AB - 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 REN
KCTD11/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.
KW - Cancer
KW - Chfr
KW - DBC1
KW - HDAC inhibitors
KW - HDACs
KW - HIC1
KW - REN
UR - http://www.scopus.com/inward/record.url?scp=79951713773&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79951713773&partnerID=8YFLogxK
U2 - 10.1016/j.bbcan.2011.01.002
DO - 10.1016/j.bbcan.2011.01.002
M3 - Article
C2 - 21277938
AN - SCOPUS:79951713773
VL - 1815
SP - 241
EP - 252
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
SN - 0304-419X
IS - 2
ER -