Chromatin assembly factor 1 suppresses epigenetic reprogramming toward adaptive drug resistance.
J Natl Cancer Cent
; 1(1): 15-22, 2021 Mar.
Article
em En
| MEDLINE
| ID: mdl-39036786
ABSTRACT
The long-term effectiveness of targeted cancer therapies is limited by the development of resistance. Although epigenetic reprogramming has been implicated in resistance, the mechanisms remain elusive. Herein, we demonstrate that increased chromatin accessibility is involved in adaptive BRAF inhibitor (BRAFi)-resistance in melanoma cells. We observed loss of chromatin assembly factor 1 (CAF-1) and its related histone H3 lysine 9 trimethylation (H3K9me3) with adaptive BRAFi resistance. We further showed that depletion of CAF-1 provides chromatin plasticity for effective reprogramming by AP1 components to promote BRAFi resistance. Our data suggest that therapeutic approaches to restore H3K9me3 levels may compensate for the loss of CAF-1 and, in turn, suppress resistance to BRAF inhibitors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
J Natl Cancer Cent
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos