Signalling pathways in UHRF1-dependent regulation of tumor suppressor genes in cancer.
Fiche publication
Date publication
novembre 2016
Journal
Journal of experimental & clinical cancer research : CR
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BRONNER Christian, Dr MOUSLI Marc
Tous les auteurs :
Alhosin M, Omran Z, Zamzami MA, Al-Malki AL, Choudhry H, Mousli M, Bronner C
Lien Pubmed
Résumé
Epigenetic silencing of tumor suppressor genes (TSGs) through DNA methylation and histone changes is a main hallmark of cancer. Ubiquitin-like with PHD and RING Finger domains 1 (UHRF1) is a potent oncogene overexpressed in various solid and haematological tumors and its high expression levels are associated with decreased expression of several TSGs including p16 (INK4A) , BRCA1, PPARG and KiSS1. Using its several functional domains, UHRF1 creates a strong coordinated dialogue between DNA methylation and histone post-translation modification changes causing the epigenetic silencing of TSGs which allows cancer cells to escape apoptosis. To ensure the silencing of TSGs during cell division, UHRF1 recruits several enzymes including histone deacetylase 1 (HDAC1), DNA methyltransferase 1 (DNMT1) and histone lysine methyltransferases G9a and Suv39H1 to the right place at the right moment. Several in vitro and in vivo works have reported the direct implication of the epigenetic player UHRF1 in tumorigenesis through the repression of TSGs expression and suggested UHRF1 as a promising target for cancer treatment. This review describes the molecular mechanisms underlying UHRF1 regulation in cancer and discusses its importance as a therapeutic target to induce the reactivation of TSGs and subsequent apoptosis.
Référence
J. Exp. Clin. Cancer Res.. 2016 Nov;35(1):174