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Downregulation of Dkk3 activates {beta}-catenin/TCF-4 signaling in lung cancer.
- Source :
- Carcinogenesis; Jan2008, Vol. 29 Issue 1, p84-84, 1p
- Publication Year :
- 2008
-
Abstract
- Although the oncogenic role of the Wnt/β-catenin pathway is well defined, it remains unclear how this pathway is aberrantly activated in lung cancer. We found that Dickkopf (Dkk)-3, a member of Dkk family of Wnt antagonists, is frequently inactivated in lung cancer and plays a role in suppressing lung cancer cell growth through inhibition of β-catenin/T-cell factor (TCF)-4 signaling. Dkk3 is the only Dkk family member abundantly expressed in normal lung, but silenced by promoter hypermethylation in a large fraction of lung cancer cell lines and lung tumors. Downregulation of Dkk3 was correlated with tumor progression and expression of nuclear β-catenin in lung tumors. Ectopic expression of Dkk3 in lung cancer cells with Dkk3 hypermethylation induced apoptosis and inhibited TCF-4 activity as well as nuclear accumulation of β-catenin and expression of TCF-4 targets c-Myc and cyclin D1. Furthermore, small interference RNA knock down of Dkk3 in cells lacking Dkk3 hypermethylation was sufficient to promote cell proliferation, β-catenin nuclear translocation and expression of c-Myc. These observations suggested that epigenetic inactivation of Dkk3 activates the Wnt/β-catenin pathway, thereby promoting the growth of lung cancer cells. [ABSTRACT FROM AUTHOR]
- Subjects :
- LUNGS
LUNG cancer
CELLS
OVUM
Subjects
Details
- Language :
- English
- ISSN :
- 01433334
- Volume :
- 29
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 28865924
- Full Text :
- https://doi.org/10.1093/carcin/bgm267