Junctional adhesion molecule-A, an epithelial-mesenchymal transition inducer, correlates with metastasis and poor prognosis in human nasopharyngeal cancer

Carcinogenesis. 2015 Jan;36(1):41-8. doi: 10.1093/carcin/bgu230. Epub 2014 Nov 21.

Abstract

Junctional adhesion molecule-A (JAM-A) is preferentially concentrated at tight junctions and influences epithelial cell morphology and migration. Epithelial-to-mesenchymal transition (EMT) is the conversion process of epithelial cells into mesenchymal cells, and it plays an important role in the invasiveness and metastasis of various cancers. However, the role of JAM-A in regulating the invasive behaviours of human nasopharyngeal carcinoma (NPC) is unknown. In this study, we found that JAM-A upregulation induced EMT, whereas silencing of endogenous JAM-A expression reversed EMT. Furthermore, upregulation of JAM-A led to EMT via activation phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. PI3K inhibitors blocked JAM-A-induced EMT, suggesting that the kinase acts downstream of JAM-A. Finally, results from 172 human patients with NPC showed that high expression levels of JAM-A correlated with metastasis and poor prognosis in NPC. Taken together, these results suggest that high JAM-A expression positively correlates with poor prognosis in patients with NPC, and induces EMT of NPC cells in vitro and in vivo via the PI3K/Akt pathway. These data indicate novel functions in the JAM-A repertoire, and have clinical implications for the treatment of patients with NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Proliferation / radiation effects
  • Epithelial-Mesenchymal Transition*
  • Female
  • Fluorescent Antibody Technique
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary*
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering / genetics
  • Radiation Tolerance
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Cell Adhesion Molecules
  • F11R protein, human
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt