Aberrant activation of Wingless-type (Wilt) signaling pathway plays a critical role in oncogenesis of various human cancers. Wilt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wilt signaling and acts through direct binding to Wilt in the extracellular space. Recently, we reported Wilt 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 nasopharyngcal carcinoma (NPC) cell lines. Futhermore, 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 Wilt 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. (c) 2006 Elsevier Inc. All rights reserved.