Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines.
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.
Lin
Yu-Ching
YC
Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
You
Liang
L
Xu
Zhidong
Z
He
Biao
B
Mikami
Iwao
I
Thung
Elaine
E
Chou
Josephine
J
Kuchenbecker
Kristopher
K
Kim
Jae
J
Raz
Dan
D
Yang
Cheng-Ta
CT
Chen
Jan-Kan
JK
Jablons
David M
DM
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*
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