NAG7 promotes human nasopharyngeal carcinoma invasion through inhibition of estrogen receptor alpha and up-regulation of JNK2/AP-1/MMP1 pathways

J Cell Physiol. 2009 Nov;221(2):394-401. doi: 10.1002/jcp.21867.

Abstract

The NAG7, an estrogen receptor repressor, is a negative regulator of nasopharyngeal carcinoma cell growth. Here, we report that NAG7 promotes human nasopharyngeal carcinoma invasion, and we identify the mechanisms underlying this function. As a consequence of elevated NAG7 expression, the adhesion, migration, and invasive capabilities of HNE1 cells in vitro and in vivo were enhanced. NAG7 was a significant negative regulator of protein expression of estrogen receptor alpha (ERalpha), and activated both the JNK2/AP-1/MMP1 and the upstream H-Ras/p-c-Raf pathways. None of these effects induced by NAG7 over-expression could be counteracted by estrogen. These observations indicate that NAG7 plays a potential role in promoting nasopharyngeal carcinoma invasion by regulation of ERalpha and the H-ras/p-c-Raf and JNK2/AP-1/MMP1 signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / antagonists & inhibitors*
  • Estrogen Receptor alpha / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Matrix Metalloproteinase 1 / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mitogen-Activated Protein Kinase 9 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 9 / metabolism
  • Nasopharyngeal Neoplasms / enzymology*
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / pathology*
  • Neoplasm Invasiveness / pathology*
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-raf / metabolism
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Signal Transduction* / drug effects
  • Transcription Factor AP-1 / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Up-Regulation* / drug effects

Substances

  • Cell Cycle Proteins
  • Estrogen Receptor alpha
  • LINC00312 long non-coding RNA, human
  • Membrane Proteins
  • Protein Kinase Inhibitors
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Transcription Factor AP-1
  • Tumor Suppressor Proteins
  • Estradiol
  • Mitogen-Activated Protein Kinase 9
  • Proto-Oncogene Proteins c-raf
  • Matrix Metalloproteinase 1
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)