Back to Search
Start Over
Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma
- Source :
- Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-17 (2021), Signal Transduction and Targeted Therapy
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group, 2021.
-
Abstract
- Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been lagging. Nasopharyngeal carcinoma (NPC) is a distinctive cancer with poor differentiation and high prevalence of Epstein-Barr virus (EBV) infection. Here, we show that the expression of EBV latent protein LMP1 induces dedifferentiated and stem-like status with high plasticity through the transcriptional inhibition of CEBPA. Mechanistically, LMP1 upregulates STAT5A and recruits HDAC1/2 to the CEBPA locus to reduce its histone acetylation. HDAC inhibition restored CEBPA expression, reversing cellular dedifferentiation and stem-like status in mouse xenograft models. These findings provide a novel mechanistic epigenetic-based insight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity.
- Subjects :
- Gene Expression Regulation, Viral
Cancer Research
Cellular Dedifferentiation
Epstein-Barr Virus Infections
Herpesvirus 4, Human
QH301-705.5
Cell Plasticity
Biology
Article
Viral Matrix Proteins
Mice
Differentiation therapy
Cancer stem cell
Cell Line, Tumor
CEBPA
Genetics
medicine
STAT5 Transcription Factor
Animals
Humans
Epigenetics
Biology (General)
Head and neck cancer
Nasopharyngeal Carcinoma
Cancer stem cells
Cancer
Cell Dedifferentiation
medicine.disease
Gene Expression Regulation, Neoplastic
Histone Deacetylase Inhibitors
Nasopharyngeal carcinoma
Cancer cell
Cancer research
CCAAT-Enhancer-Binding Proteins
Heterografts
Medicine
Subjects
Details
- Language :
- English
- ISSN :
- 20593635
- Volume :
- 6
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Signal Transduction and Targeted Therapy
- Accession number :
- edsair.doi.dedup.....c67de4d65bedcd8d7d6047ea25a35d46