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.

Oncogene
|November 14, 2003
PubMed

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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