title: Dickkopf-1 inhibits thyroid cancer cell survival and migration through regulation of β-catenin/E-cadherin signaling.
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.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Cho
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Lee
authors.forename: Hwanhee
authors.initials: H
authors.lastname: Kim
authors.forename: Soon Hui
authors.initials: SH
authors.lastname: Kim
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Ahn
authors.forename: Young A
authors.initials: YA
authors.lastname: Kim
authors.forename: Ka Hee
authors.initials: KH
authors.lastname: Yi
authors.forename: Do Joon
authors.initials: DJ
authors.lastname: Park
authors.forename: Chan Soo
authors.initials: CS
authors.lastname: Shin
authors.forename: Soon-Hyun
authors.initials: SH
authors.lastname: Ahn
authors.forename: Bo Youn
authors.initials: BY
authors.lastname: Cho
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
mesh_terms: D015703:Antigens, CD; D017209:Apoptosis / Q000235:genetics; D015820:Cadherins / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics / Q000378:metabolism; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C555482:LRP5 protein, human; C555475:LRP6 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D051176:beta Catenin