title: Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines.
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.
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Lin
authors.forename: Liang
authors.initials: L
authors.lastname: You
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xu
authors.forename: Biao
authors.initials: B
authors.lastname: He
authors.forename: Iwao
authors.initials: I
authors.lastname: Mikami
authors.forename: Elaine
authors.initials: E
authors.lastname: Thung
authors.forename: Josephine
authors.initials: J
authors.lastname: Chou
authors.forename: Kristopher
authors.initials: K
authors.lastname: Kuchenbecker
authors.forename: Jae
authors.initials: J
authors.lastname: Kim
authors.forename: Dan
authors.initials: D
authors.lastname: Raz
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Yang
authors.forename: Jan-Kan
authors.initials: JK
authors.lastname: Chen
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D002277:Carcinoma / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D018076:DNA, Complementary / Q000378:metabolism; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018076:DNA, Complementary; D012097:Repressor Proteins; C485569:WIF1 protein, human; D051153:Wnt Proteins; D000077209:Decitabine; D001374:Azacitidine