Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines

Biochem Biophys Res Commun. 2006 Mar 10;341(2):635-40. doi: 10.1016/j.bbrc.2005.12.220. Epub 2006 Jan 17.

Abstract

Aberrant activation of Wingless-type (Wnt) signaling pathway plays a critical role in oncogenesis of various human cancers. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and acts through direct binding to Wnt in the extracellular space. Recently, we reported Wnt signaling in various human malignancies. In addition, we identified in lung cancer that WIF-1 is silenced due to promoter hypermethylation. In this study, we found constitutive activation of Wnt signaling and WIF-1 silencing in nasopharyngeal carcinoma (NPC) cell lines. Furthermore, by utilizing methylation-specific PCR and sequence analysis, we demonstrated that frequent hypermethylation of the WIF-1 promoter correlates with WIF-1 silencing in NPC cell lines. Our results indicate that aberrant Wnt signaling is a common event in NPC carcinogenesis linked with WIF-1 silencing in at least cell lines. Strategies targeting these molecules should be potentially promising in treating NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Blotting, Western
  • Carcinoma / pathology*
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • DNA Methylation
  • DNA, Complementary / metabolism
  • Decitabine
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • Nasopharyngeal Neoplasms / pathology*
  • Promoter Regions, Genetic
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Signal Transduction*
  • Transfection
  • Wnt Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA, Complementary
  • Repressor Proteins
  • WIF1 protein, human
  • Wnt Proteins
  • Decitabine
  • Azacitidine