The critical role of the class III histone deacetylase SIRT1 in cancer.
Gene expression and deacetylase activity of the class III histone deacetylase SIRT1 are up-regulated in cancer cells due to oncogene overexpression or loss of function of tumor suppressor genes. SIRT1 induces histone deacetylation and methylation, promoter CpG island methylation, transcriptional repression, and deacetylation of tumor suppressor proteins. SIRT1 may play a critical role in tumor initiation, progression, and drug resistance by blocking senescence and apoptosis, and promoting cell growth and angiogenesis. SIRT1 inhibitors have shown promising anticancer effects in animal models of cancer. Further screening for more potent SIRT1 inhibitors may lead to compounds suitable for clinical trials in patients.
Liu
Tao
T
Children's Cancer Institute Australia for Medical Research, Sydney, New South Wales, Australia.
Liu
Pei Y
PY
Marshall
Glenn M
GM
D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D016147:Genes, Tumor Suppressor; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D009857:Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D056564:Sirtuin 1; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D004791:Enzyme Inhibitors; D006657:Histones; D012333:RNA, Messenger; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins