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:
https://lup.lub.lu.se/record/1302118
- author
- Hagerling, Catharina
LU
; Landberg, Göran
LU
; Andersson, Tommy
LU
and Leandersson, Karin
LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 284
- pages
- 10968 - 10979
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000265104600069
- pmid:19244247
- scopus:67449106155
- pmid:19244247
- 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
- 2016-04-04 07:00:27
- date last changed
- 2022-04-23 03:57:48
@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 = {{American Society for Biochemistry and Molecular Biology}},
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}},
doi = {{10.1074/jbc.M804923200}},
volume = {{284}},
year = {{2009}},
}