Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma PMID: 34482361

GLP-1 and Obesity Research

2026-08-18

Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma

Signal Transduct Target Ther. 2021 Sep 4;6(1):333. doi: 10.1038/s41392-021-00702-4.

Jiajun Xie ^# ¹ ² ³ , Zifeng Wang ^# ¹ , Wenjun Fan ^# ² , Youping Liu ^# ¹ , Fang Liu ^# ¹ , Xiangbo Wan ^# ⁴ , Meiling Liu ¹ , Xuan Wang ¹ , Deshun Zeng ¹ , Yan Wang ² , Bin He ¹ , Min Yan ¹ , Zijian Zhang ¹ , Mengjuan Zhang ² , Zhijie Hou ² , Chunli Wang ² , Zhijie Kang ² , Wenfeng Fang ¹ , Li Zhang ¹ , Eric W-F Lam ¹ , Xiang Guo ¹ , Jinsong Yan ⁵ , Yixin Zeng ⁶ , Mingyuan Chen ⁷ , Quentin Liu ⁸ ⁹ ¹⁰

Affiliations

1. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.
2. Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
3. Department of Hematology; Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine; Liaoning Medical Center for Hematopoietic Stem Cell Transplantation; Dalian Key Laboratory of Hematology; Diamond Bay Institute of Hematology, The Affiliated Second Hospital of Dalian Medical University, Dalian, China.
4. Department of Radiation Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
5. Department of Hematology; Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine; Liaoning Medical Center for Hematopoietic Stem Cell Transplantation; Dalian Key Laboratory of Hematology; Diamond Bay Institute of Hematology, The Affiliated Second Hospital of Dalian Medical University, Dalian, China. [email protected].
6. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China. [email protected].
7. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China. [email protected].
8. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China. [email protected].
9. Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China. [email protected].
10. Sun Yat-sen Institute of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. [email protected].
# Contributed equally.

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.