Journal article
Chromatin assembly factor 1 suppresses epigenetic reprogramming toward adaptive drug resistance
Journal of the National Cancer Center, Vol.1(1), pp.15-22
03/2021
DOI: 10.1016/j.jncc.2020.12.003
PMCID: PMC11256593
PMID: 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.
Details
- Title: Subtitle
- Chromatin assembly factor 1 suppresses epigenetic reprogramming toward adaptive drug resistance
- Creators
- Zhiquan Wang - Mayo ClinicRentian Wu - Mayo ClinicQian Nie - Mayo ClinicKelly J. Bouchonville - Mayo ClinicRobert B. Diasio - Mayo ClinicSteven M. Offer - Mayo Clinic
- Resource Type
- Journal article
- Publication Details
- Journal of the National Cancer Center, Vol.1(1), pp.15-22
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.jncc.2020.12.003
- PMID
- 39036786
- PMCID
- PMC11256593
- ISSN
- 2667-0054
- eISSN
- 2667-0054
- Grant note
- DOI: 10.13039/100000054, name: National Cancer Institute
- Language
- English
- Date published
- 03/2021
- Academic Unit
- Pathology
- Record Identifier
- 9984618522002771
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