Volume 6 Issue 10, Oct 2021

ISSN: 2095-9907 

EISSN: 2059-23635 

2023 impact factor 40.8 

 (Clarivate Analytics, 2024)
Volume 6 Issue 10, Oct 2021:
Article
Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma
Jiajun Xie,Zifeng Wang  ORCID: orcid.org/0000-0001-7400-5224,Wenjun Fan,Youping Liu,Fang Liu,Xiangbo Wan  ORCID: orcid.org/0000-0001-9437-6188,Meiling Liu,Xuan Wang,Deshun Zeng,Yan Wang,Bin He,Min Yan,Zijian Zhang,Mengjuan Zhang,Zhijie Hou,Chunli Wang,Zhijie Kang,Wenfeng Fang,Li Zhang,Eric W-F Lam  ORCID: orcid.org/0000-0003-1274-3576,Xiang Guo,Jinsong Yan,Yixin Zeng,Mingyuan Chen &…Quentin Liu 
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.