Dickkopf-1 inhibits thyroid cancer cell survival and migration through regulation of β-catenin/E-cadherin signaling
| Autor: | Young Joo Park, Eun Jung Lee, Sun Wook Cho, Hwan Hee Kim, Soon-Hyun Ahn, Soon Hui Kim, Bo Youn Cho, Do Joon Park, Young A. Kim, Chan Soo Shin, Ka Hee Yi, Hwa Young Ahn |
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| Rok vydání: | 2012 |
| Předmět: |
Cell Survival
Apoptosis Biology medicine.disease_cause Biochemistry Endocrinology Antigens CD Cell Movement Cell Line Tumor medicine Humans Viability assay Thyroid Neoplasms Molecular Biology Wnt Signaling Pathway beta Catenin Cell Proliferation Cell growth Cadherin Carcinoma Wnt signaling pathway Cell migration Cadherins Carcinoma Papillary Cell biology Gene Expression Regulation Neoplastic Low Density Lipoprotein Receptor-Related Protein-5 Thyroid Cancer Papillary Catenin Low Density Lipoprotein Receptor-Related Protein-6 Intercellular Signaling Peptides and Proteins Carcinogenesis Signal Transduction |
| Zdroj: | Molecular and cellular endocrinology. 366(1) |
| ISSN: | 1872-8057 |
| Popis: | Wnt/β-catenin signaling plays a role in tumorigenesis of human papillary thyroid cancer (PTC). Dickkopf-1 (Dkk-1) is an inhibitor of Wnt/β-catenin signaling. We investigated the therapeutic potential of Dkk-1 in human PTC cell lines, SNU-790, B-CPAP, and BHP10-3. Dkk-1 reversed the aberrant expression of β-catenin from nucleus to membrane and inhibited basal levels of TCF/LEF-dependent transcriptional activities. Furthermore, Dkk-1 inhibited cell viability in a dose-dependent manner and adenoviral transduction of constitutively active β-catenin blocked these effects, thus suggesting that the Dkk-1 anti-tumoral effect is mediated by Wnt/β-catenin signaling. Bromodeoxyuridine assay showed minimal effects of Dkk-1 on cell proliferation. Flow cytometric analysis with Annexin V staining showed marked induction of cell apoptosis by Dkk-1 treatment. Dkk-1 also restored the loss of membranous E-cadherin expression with consequent inhibition of cell migration and invasion. In conclusion, Dkk-1 inhibited the survival and migration of human PTC cells by regulating Wnt/β-catenin signaling and E-cadherin expression. |
| Databáze: | OpenAIRE |
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