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Updated: Aug 30, 2026

Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
Published on: September 28, 2022
RECK is a target of Epstein-Barr virus latent membrane protein 1
Li-Teh Liu1, Jyh-Ping Peng, Hui-Chiu Chang
1Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
Abstract:
Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) has been suggested to be involved in tumor metastasis. However, the molecular mechanism of LMP1-induced metastasis is largely unknown. In this study, we investigated the effect of LMP1 on the expression of RECK, a metastasis suppressor gene, in an EBV-negative nasopharyngeal carcinoma (NPC) cell line. Our data demonstrated that LMP1 induced downregulation of RECK via transcription repression in TW04 cells. In addition, we found that LMP1 acted via an Sp1 site to inhibit RECK promoter activity. We next studied the signaling pathway that mediated the effect of LMP1 on RECK expression. Our results showed that LMP1 potently stimulated the activity of extracellular signal-regulated kinases (ERKs) and inhibition of ERK activity by PD98059 antagonized LMP1-induced downregulation of RECK. Conversely, the c-Jun N-terminal kinase inhibitor SP600125 and p38(HOG) kinase inhibitor SB203580 had little effect. We also found that the expression of LMP1 increased the invasive ability of TW04 cells. The importance of RECK in LMP1-induced invasiveness was supported by three observations. First, restoration of RECK expression by PD98059 reduced LMP1-induced release of active MMP-9. Second, suppression of PD98059-induced RECK expression by small interference RNA abolished the inhibitory action of PD98059 on LMP1-induced invasiveness. Third, coexpression of RECK with LMP1 in TW04 cells effectively suppressed cell invasiveness induced by LMP1. Taken together, these results suggest that LMP1 inhibits RECK expression via the ERK/Sp1 signaling pathway and this inhibition is a critical step for LMP1-induced tumor metastasis.
Insights
Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) promotes tumor metastasis by downregulating the RECK suppressor gene through the ERK/Sp1 pathway. Restoring RECK expression inhibits LMP1-induced cell invasion.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is implicated in tumor metastasis.
- The precise molecular mechanisms underlying LMP1-driven metastasis remain largely unelucidated.
Purpose of the Study:
- To investigate the impact of LMP1 on RECK gene expression in nasopharyngeal carcinoma (NPC) cells.
- To elucidate the signaling pathways involved in LMP1-mediated regulation of RECK and its role in metastasis.
Main Methods:
- Analysis of RECK expression and promoter activity in EBV-negative NPC cells (TW04) with and without LMP1 expression.
- Utilized pharmacological inhibitors for extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase.
- Assessed cell invasiveness and matrix metalloproteinase-9 (MMP-9) activity.
- Employed small interfering RNA (siRNA) to suppress RECK expression.
Main Results:
- LMP1 significantly downregulated RECK expression via transcriptional repression, involving an Sp1 binding site in the RECK promoter.
- LMP1 activated the ERK signaling pathway, which was crucial for RECK downregulation; inhibiting ERK restored RECK levels.
- LMP1 enhanced TW04 cell invasiveness, which was attenuated by restoring RECK expression, demonstrating RECK's critical role in mediating LMP1-induced metastasis.
Conclusions:
- LMP1 inhibits RECK expression through the ERK/Sp1 signaling pathway in NPC cells.
- The downregulation of RECK by LMP1 is a key mechanism contributing to tumor metastasis.
- Targeting the ERK/Sp1/RECK axis presents a potential therapeutic strategy for EBV-associated cancers.
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