Advanced

WNT-5a-CKIalpha signaling promotes beta -catenin/E-cadherin complex formation and intercellular adhesion in human breast epithelial cells.

Hagerling, Catharina LU ; Landberg, Göran LU ; Andersson, Tommy LU and Leandersson, Karin LU (2009) In Journal of Biological Chemistry 284. p.10968-10979
Abstract
Wnt-5a is a non-transforming Wnt protein that is implicated in cell-polarity, adhesion and motility. We have previously shown that low expression of Wnt-5a is a predictor of shorter disease-free survival in human breast cancer. Here, we investigated whether ss-catenin/E-cadherin mediated cell-cell adhesion was affected by loss of Wnt-5a in breast carcinomas, thereby promoting a metastatic behavior of the tumor. We show that Wnt-5a stimulation of human breast epithelial cells leads to an increased Ca2+-dependent cell-cell adhesion. Furthermore, Wnt-5a/Casein Kinase Ia (CKIa)-specific Ser45-phosphorylation of ss-catenin is associated with an increased complex formation of ss-catenin/E-cadherin. Mutation of Ser45 decreases the... (More)
Wnt-5a is a non-transforming Wnt protein that is implicated in cell-polarity, adhesion and motility. We have previously shown that low expression of Wnt-5a is a predictor of shorter disease-free survival in human breast cancer. Here, we investigated whether ss-catenin/E-cadherin mediated cell-cell adhesion was affected by loss of Wnt-5a in breast carcinomas, thereby promoting a metastatic behavior of the tumor. We show that Wnt-5a stimulation of human breast epithelial cells leads to an increased Ca2+-dependent cell-cell adhesion. Furthermore, Wnt-5a/Casein Kinase Ia (CKIa)-specific Ser45-phosphorylation of ss-catenin is associated with an increased complex formation of ss-catenin/E-cadherin. Mutation of Ser45 decreases the ss-catenin/E-cadherin association. Also, the inhibitory effect of Wnt-5a on breast epithelial cell invasion is reduced upon mutation of ss-catenin-Ser45. The Wnt-5a-CKIa induced Ser45-phosphorylation does not lead to degradation of ss-catenin. Finally we show that human breast cancers lacking Wnt-5a protein have a significantly lower level of membrane-associated ss-catenin. Downregulation of Wnt-5a expression and subsequent reduction of membrane-associated ss-catenin in invasive breast cancer, can therefore contribute to a decreased cell-cell adhesion and increased motility resulting in a higher probability for metastatic disease. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
284
pages
10968 - 10979
publisher
ASBMB
external identifiers
  • wos:000265104600069
  • pmid:19244247
  • scopus:67449106155
ISSN
1083-351X
DOI
10.1074/jbc.M804923200
language
English
LU publication?
yes
id
8822c395-32b4-4c34-add0-dd7da72ed804 (old id 1302118)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19244247?dopt=Abstract
date added to LUP
2009-03-09 13:07:23
date last changed
2017-12-10 04:40:46
@article{8822c395-32b4-4c34-add0-dd7da72ed804,
  abstract     = {Wnt-5a is a non-transforming Wnt protein that is implicated in cell-polarity, adhesion and motility. We have previously shown that low expression of Wnt-5a is a predictor of shorter disease-free survival in human breast cancer. Here, we investigated whether ss-catenin/E-cadherin mediated cell-cell adhesion was affected by loss of Wnt-5a in breast carcinomas, thereby promoting a metastatic behavior of the tumor. We show that Wnt-5a stimulation of human breast epithelial cells leads to an increased Ca2+-dependent cell-cell adhesion. Furthermore, Wnt-5a/Casein Kinase Ia (CKIa)-specific Ser45-phosphorylation of ss-catenin is associated with an increased complex formation of ss-catenin/E-cadherin. Mutation of Ser45 decreases the ss-catenin/E-cadherin association. Also, the inhibitory effect of Wnt-5a on breast epithelial cell invasion is reduced upon mutation of ss-catenin-Ser45. The Wnt-5a-CKIa induced Ser45-phosphorylation does not lead to degradation of ss-catenin. Finally we show that human breast cancers lacking Wnt-5a protein have a significantly lower level of membrane-associated ss-catenin. Downregulation of Wnt-5a expression and subsequent reduction of membrane-associated ss-catenin in invasive breast cancer, can therefore contribute to a decreased cell-cell adhesion and increased motility resulting in a higher probability for metastatic disease.},
  author       = {Hagerling, Catharina and Landberg, Göran and Andersson, Tommy and Leandersson, Karin},
  issn         = {1083-351X},
  language     = {eng},
  pages        = {10968--10979},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {WNT-5a-CKIalpha signaling promotes beta -catenin/E-cadherin complex formation and intercellular adhesion in human breast epithelial cells.},
  url          = {http://dx.doi.org/10.1074/jbc.M804923200},
  volume       = {284},
  year         = {2009},
}