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Wnt-5a has tumor suppressor activity in thyroid carcinoma

Kremenevskaja, N; von Wasielewski, R; Rao, AS; Schofl, C; Andersson, Tommy LU and Brabant, G (2005) In Oncogene 24(13). p.2144-2154
Abstract
Stabilization of beta-catenin by inhibition of its phosphorylation is characteristic of an activation of the canonical Wnt/beta-catenin signaling pathway and is associated with various human carcinomas. It contrasts to an as yet incompletely characterized action of an alternative noncanonical Wnt signaling pathway on neoplastic transformation. The aim of the present study was to test the effects of a member of the noncanonical Wnt signaling pathway, Wnt-5a, in primary thyroid carcinomas and in thyroid carcinoma cell lines. Compared to normal tissue Wnt-5a mRNA expression was clearly increased in thyroid carcinomas. Immunohistochemically, a bell-shaped response was observed with low to undetectable levels in normal tissue and in anaplastic... (More)
Stabilization of beta-catenin by inhibition of its phosphorylation is characteristic of an activation of the canonical Wnt/beta-catenin signaling pathway and is associated with various human carcinomas. It contrasts to an as yet incompletely characterized action of an alternative noncanonical Wnt signaling pathway on neoplastic transformation. The aim of the present study was to test the effects of a member of the noncanonical Wnt signaling pathway, Wnt-5a, in primary thyroid carcinomas and in thyroid carcinoma cell lines. Compared to normal tissue Wnt-5a mRNA expression was clearly increased in thyroid carcinomas. Immunohistochemically, a bell-shaped response was observed with low to undetectable levels in normal tissue and in anaplastic tumors whereas differentiated thyroid carcinomas showed strong positive immunostaining for Wnt-5a. Transfection of Wnt-5a in a thyroid tumor cell line FTC-133 was able to reduce proliferation, migration, invasiveness and clonogenicity in these cells. These effects of Wnt-5a are associated with membranous b-catenin translocation and c-myc oncogene suppression and are mediated through an increase in intracellular Ca2+ release, which via CaMKII pathways promotes beta-catenin phosphorylation. Specific inhibition of beta-catenin phosphorylation by W-7, a calmodulin inhibitor, or by KN-93, a CaMKII inhibitor, supports these. findings whereas PKC inhibitors were without effect. This interaction occurs downstream of GSK-3 beta as no Wnt-5a effect was seen on the Ser(9) phosphorylation of GSK-3 beta. Our data are compatible with the hypothesis that Wnt-5a serves as an antagonist to the canonical Wnt- signaling pathway with tumor suppressor activity in differentiated thyroid carcinomas. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Wnt, beta-catenin, tumor suppression, thyroid cancer
in
Oncogene
volume
24
issue
13
pages
2144 - 2154
publisher
Nature Publishing Group
external identifiers
  • wos:000227857900002
  • pmid:15735754
  • scopus:16444372007
ISSN
1476-5594
DOI
10.1038/sj.onc.1208370
language
English
LU publication?
yes
id
93573fd9-1693-4c91-be5a-fd307f6e202b (old id 896996)
date added to LUP
2008-01-16 13:16:54
date last changed
2017-11-05 03:41:46
@article{93573fd9-1693-4c91-be5a-fd307f6e202b,
  abstract     = {Stabilization of beta-catenin by inhibition of its phosphorylation is characteristic of an activation of the canonical Wnt/beta-catenin signaling pathway and is associated with various human carcinomas. It contrasts to an as yet incompletely characterized action of an alternative noncanonical Wnt signaling pathway on neoplastic transformation. The aim of the present study was to test the effects of a member of the noncanonical Wnt signaling pathway, Wnt-5a, in primary thyroid carcinomas and in thyroid carcinoma cell lines. Compared to normal tissue Wnt-5a mRNA expression was clearly increased in thyroid carcinomas. Immunohistochemically, a bell-shaped response was observed with low to undetectable levels in normal tissue and in anaplastic tumors whereas differentiated thyroid carcinomas showed strong positive immunostaining for Wnt-5a. Transfection of Wnt-5a in a thyroid tumor cell line FTC-133 was able to reduce proliferation, migration, invasiveness and clonogenicity in these cells. These effects of Wnt-5a are associated with membranous b-catenin translocation and c-myc oncogene suppression and are mediated through an increase in intracellular Ca2+ release, which via CaMKII pathways promotes beta-catenin phosphorylation. Specific inhibition of beta-catenin phosphorylation by W-7, a calmodulin inhibitor, or by KN-93, a CaMKII inhibitor, supports these. findings whereas PKC inhibitors were without effect. This interaction occurs downstream of GSK-3 beta as no Wnt-5a effect was seen on the Ser(9) phosphorylation of GSK-3 beta. Our data are compatible with the hypothesis that Wnt-5a serves as an antagonist to the canonical Wnt- signaling pathway with tumor suppressor activity in differentiated thyroid carcinomas.},
  author       = {Kremenevskaja, N and von Wasielewski, R and Rao, AS and Schofl, C and Andersson, Tommy and Brabant, G},
  issn         = {1476-5594},
  keyword      = {Wnt,beta-catenin,tumor suppression,thyroid cancer},
  language     = {eng},
  number       = {13},
  pages        = {2144--2154},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {Wnt-5a has tumor suppressor activity in thyroid carcinoma},
  url          = {http://dx.doi.org/10.1038/sj.onc.1208370},
  volume       = {24},
  year         = {2005},
}