Dickkopf-1 inhibits thyroid cancer cell survival and migration through regulation of β-catenin/E-cadherin signaling

Sun Wook Cho; Eun Jung Lee; Hwanhee Kim; Soon Hui Kim; Hwa Young Ahn; Young A Kim; Ka Hee Yi; Do Joon Park; Chan Soo Shin; Soon-Hyun Ahn; Bo Youn Cho; Young Joo Park

doi:10.1016/j.mce.2012.12.007

Dickkopf-1 inhibits thyroid cancer cell survival and migration through regulation of β-catenin/E-cadherin signaling

Mol Cell Endocrinol. 2013 Feb 5;366(1):90-8. doi: 10.1016/j.mce.2012.12.007. Epub 2012 Dec 20.

Authors

Sun Wook Cho¹, Eun Jung Lee, Hwanhee Kim, Soon Hui Kim, Hwa Young Ahn, Young A Kim, Ka Hee Yi, Do Joon Park, Chan Soo Shin, Soon-Hyun Ahn, Bo Youn Cho, Young Joo Park

Affiliation

¹ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

PMID: 23261982
DOI: 10.1016/j.mce.2012.12.007

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, CD
Apoptosis / genetics
Cadherins / metabolism*
Carcinoma / genetics
Carcinoma / metabolism*
Carcinoma / pathology*
Carcinoma, Papillary
Cell Line, Tumor
Cell Movement* / genetics
Cell Proliferation
Cell Survival / genetics
Gene Expression Regulation, Neoplastic
Humans
Intercellular Signaling Peptides and Proteins / genetics
Intercellular Signaling Peptides and Proteins / metabolism*
Low Density Lipoprotein Receptor-Related Protein-5 / genetics
Low Density Lipoprotein Receptor-Related Protein-5 / metabolism
Low Density Lipoprotein Receptor-Related Protein-6 / genetics
Low Density Lipoprotein Receptor-Related Protein-6 / metabolism
Signal Transduction* / genetics
Thyroid Cancer, Papillary
Thyroid Neoplasms / genetics
Thyroid Neoplasms / metabolism*
Thyroid Neoplasms / pathology*
Wnt Signaling Pathway / genetics
beta Catenin / metabolism*

Substances

Antigens, CD
CDH1 protein, human
Cadherins
DKK1 protein, human
Intercellular Signaling Peptides and Proteins
LRP5 protein, human
LRP6 protein, human
Low Density Lipoprotein Receptor-Related Protein-5
Low Density Lipoprotein Receptor-Related Protein-6
beta Catenin