TEL2 suppresses metastasis by down-regulating SERPINE1 in nasopharyngeal carcinoma

Oncotarget. 2015 Oct 6;6(30):29240-53. doi: 10.18632/oncotarget.5074.

Abstract

Metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). However, the molecular mechanisms of NPC metastasis are poorly understood. Here, using our customized gene microarray containing all of the known human transcription factors and the current markers for epithelial-mesenchymal transition, we report that TEL2 was down-regulated in highly metastatic NPC cells and the metastatic tissues in lymph node. Mechanistically, TEL2 inhibits the cell migration and invasion in vitro and metastasis in vivo by directly suppressing the SERPINE1 promoter in NPC. Consistently, an inverse correlation was observed between the protein levels of TEL2 and SERPINE1 using clinical NPC samples. Collectively, we have provided the first evidence that TEL2 plays a key role in NPC metastasis by directly down-regulating SERPINE1, and that this novel axis of TEL2 / SERPINE1 may be valuable to develop new strategies for treating NPC patients with metastasis.

Keywords: SERPINE1; TEL2; metastasis; nasopharyngeal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Base Sequence
  • Binding Sites
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / mortality
  • Carcinoma / secondary
  • Carcinoma / therapy
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation
  • Child
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Mice, Nude
  • Middle Aged
  • Molecular Sequence Data
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / therapy
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-ets / genetics
  • Proto-Oncogene Proteins c-ets / metabolism*
  • RNA Interference
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Burden
  • Young Adult

Substances

  • ETV7 protein, human
  • Plasminogen Activator Inhibitor 1
  • Proto-Oncogene Proteins c-ets
  • SERPINE1 protein, human