Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Pathol
2013 Jun 01;2302:194-204. doi: 10.1002/path.4073.
Show Gene links
Show Anatomy links
Epigenetic regulation of DACT2, a key component of the Wnt signalling pathway in human lung cancer.
Jia Y
,
Yang Y
,
Brock MV
,
Zhan Q
,
Herman JG
,
Guo M
.
???displayArticle.abstract???
Dapper, Dishevelled-associated antagonist of β-catenin (DACT), is involved in Xenopus embryonic development. Human DACT2 is localized on chromosome 6q27, a region of frequent loss of heterozygosity (LOH) in human cancers. However, the function and regulation of DACT2 in human lung cancer remain unclear. DNA sequencing, methylation-specific PCR (MSP), semi-quantitative RT-PCR, western blotting, and xenograft models were employed in this study. Eight lung cancer cell lines, 106 cases of primary lung cancer, four specimens of normal lung from patients without cancer, and 99 blood samples from healthy individuals were examined. We found that while there was no SNP related to lung cancer, the DACT2 promoter region is frequently methylated in human lung cancer. DACT2 is silenced by promoter region hypermethylation and re-expressed by 5-aza-2'-deoxyazacytidine treatment of lung cancer cell lines. Methylation of DACT2 was associated with poor differentiation of lung cancer. Loss of DACT2 expression was associated with promoter region hypermethylation in primary lung cancer, and was associated with increased β-catenin expression. Restoration of DACT2 expression suppressed tumour proliferation both in vitro and in vivo. DACT2 expression was down-regulated by siRNA knockdown in H727 cells. DACT2 inhibited T-cell factor/lymphoid enhancer factor (TCF/LEF) and its downstream genes. In conclusion, DACT2 methylation is a potential lung cancer detection marker. DACT2 is regulated by promoter region hypermethylation. DACT2 inhibits lung cancer proliferation by suppressing the Wnt signalling pathway in lung cancer.
Cheyette,
Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation.
2002, Pubmed,
Xenbase
Cheyette,
Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation.
2002,
Pubmed
,
Xenbase
Ferlay,
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.
2010,
Pubmed
Fisher,
Three Dact gene family members are expressed during embryonic development and in the adult brains of mice.
2006,
Pubmed
Gao,
[Genescan analysis of non-small cell lung cancer in the long arm of chromosome 6].
2002,
Pubmed
Girard,
Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering.
2000,
Pubmed
Griffiths,
DNA methyltransferase and histone deacetylase inhibitors in the treatment of myelodysplastic syndromes.
2008,
Pubmed
Han,
Nuclear Receptor Interaction Protein (NRIP) expression assay using human tissue microarray and immunohistochemistry technology confirming nuclear localization.
2008,
Pubmed
Herman,
Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands.
1996,
Pubmed
Jemal,
Global cancer statistics.
2011,
Pubmed
Jia,
SOX17 antagonizes WNT/β-catenin signaling pathway in hepatocellular carcinoma.
2010,
Pubmed
Jiang,
DACT3 is an epigenetic regulator of Wnt/beta-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications.
2008,
Pubmed
Katoh,
Identification and characterization of human DAPPER1 and DAPPER2 genes in silico.
2003,
Pubmed
,
Xenbase
Kettunen,
Dact1-3 mRNAs exhibit distinct expression domains during tooth development.
2010,
Pubmed
Kivimäe,
All Dact (Dapper/Frodo) scaffold proteins dimerize and exhibit conserved interactions with Vangl, Dvl, and serine/threonine kinases.
2011,
Pubmed
Korinek,
Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.
1997,
Pubmed
Lewis,
Prediction of mammalian microRNA targets.
2003,
Pubmed
Li,
MicroRNA-101 regulates expression of the v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinoma.
2009,
Pubmed
Licchesi,
Epigenetic alteration of Wnt pathway antagonists in progressive glandular neoplasia of the lung.
2008,
Pubmed
Liu,
Paired box gene 5 is a novel tumor suppressor in hepatocellular carcinoma through interaction with p53 signaling pathway.
2011,
Pubmed
Maemondo,
Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.
2010,
Pubmed
Morin,
Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC.
1997,
Pubmed
Qin,
Mechanisms of resistance to 5-aza-2'-deoxycytidine in human cancer cell lines.
2009,
Pubmed
Shih,
The beta-catenin binding domain of adenomatous polyposis coli is sufficient for tumor suppression.
2000,
Pubmed
Soria,
EGFR-mutated oncogene-addicted non-small cell lung cancer: current trends and future prospects.
2012,
Pubmed
Steinemann,
Identification of candidate tumor-suppressor genes in 6q27 by combined deletion mapping and electronic expression profiling in lymphoid neoplasms.
2003,
Pubmed
Su,
The evolutionally conserved activity of Dapper2 in antagonizing TGF-beta signaling.
2007,
Pubmed
,
Xenbase
Teran,
Dpr Acts as a molecular switch, inhibiting Wnt signaling when unphosphorylated, but promoting Wnt signaling when phosphorylated by casein kinase Idelta/epsilon.
2009,
Pubmed
,
Xenbase
Wilk,
Linkage and association with pulmonary function measures on chromosome 6q27 in the Framingham Heart Study.
2003,
Pubmed
Yau,
HDPR1, a novel inhibitor of the WNT/beta-catenin signaling, is frequently downregulated in hepatocellular carcinoma: involvement of methylation-mediated gene silencing.
2005,
Pubmed
,
Xenbase
Yu,
AKT signaling pathway activated by HIN-1 methylation in non-small cell lung cancer.
2012,
Pubmed