Epstein-Barr virus latent membrane protein-1 upregulates autophagy and promotes viability in Hodgkin lymphoma: Implications for targeted therapy

Hui Chen Lin, Yao Chang, Ruo Yu Chen, Liang Yi Hung, Paul Chih Hsueh Chen, Ya Ping Chen, L. Jeffrey Medeiros, Po Min Chiang, Kung Chao Chang

研究成果: Article同行評審

摘要

Hodgkin lymphoma (HL) is composed of neoplastic Hodgkin and Reed-Sternberg cells in an inflammatory background. The neoplastic cells are derived from germinal center B cells that, in most cases, are infected by Epstein-Barr virus (EBV), which may play a role in tumorigenesis. Given that EBV-latent membrane protein 1 (LMP1) regulates autophagy in B cells, we explored the role of autophagy mediated by EBV or LMP1 in HL. We found that EBV-LMP1 transfection in HL cells induced a modest increase in autophagy signals, attenuated starvation-induced autophagic stress, and alleviated autophagy inhibition- or doxorubicin-induced cell death. LMP1 knockdown leads to decreased autophagy LC3 signals. A xenograft mouse model further showed that EBV infection significantly increased expression of the autophagy marker LC3 in HL cells. Clinically, LC3 was expressed in 15% (19/127) of HL samples, but was absent in all cases of nodular lymphocyte-predominant and lymphocyte-rich classic HL cases. Although expression of LC3 was not correlated with EBV status or clinical outcome, autophagic blockade effectively eradicated LMP1-positive HL xenografts with better efficacy than LMP1-negative HL xenografts. Collectively, these results suggest that EBV-LMP1 enhances autophagy and promotes the viability of HL cells. Autophagic inhibition may be a potential therapeutic strategy for treating patients with HL, especially EBV-positive cases.

原文English
頁(從 - 到)1589-1602
頁數14
期刊Cancer Science
112
發行號4
DOIs
出版狀態Published - 2021 四月

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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