Repression of Wnt-5a impairs DDR1 phosphorylation and modifies adhesion and migration of mammary cells
(2001) In Journal of Cell Science 114(Pt 11). p.2043-2053- Abstract
- The Wnt-5a gene encodes a secreted protein that controls several normal processes during embryogenesis and development of adult tissues by as yet unknown mechanisms. Endogenous expression of Wnt-5a mRNA is known to occur in both mouse and human mammary cell lines. To investigate the biological role of Wnt-5a in the human mammary epithelial cell line HB2, we used an antisense approach to repress endogenous expression of Wnt-5a protein. We also generated a cell population that constitutively overexpresses this protein. We found that overexpression of Wnt-5a protein enhanced cell-to-collagen binding and abolished hepatocyte growth factor-stimulated migration of HB2 transfectants through collagen matrices. Conversely, repression of Wnt-5a... (More)
- The Wnt-5a gene encodes a secreted protein that controls several normal processes during embryogenesis and development of adult tissues by as yet unknown mechanisms. Endogenous expression of Wnt-5a mRNA is known to occur in both mouse and human mammary cell lines. To investigate the biological role of Wnt-5a in the human mammary epithelial cell line HB2, we used an antisense approach to repress endogenous expression of Wnt-5a protein. We also generated a cell population that constitutively overexpresses this protein. We found that overexpression of Wnt-5a protein enhanced cell-to-collagen binding and abolished hepatocyte growth factor-stimulated migration of HB2 transfectants through collagen matrices. Conversely, repression of Wnt-5a protein led to cell scattering, impaired cell-collagen interaction and enhanced cell motility. As we were searching for modified collagen receptors in antisense cells, we discovered that the collagen-binding discoidin domain receptor 1 (DDR1) failed to undergo phosphorylation. In reciprocal experiments, phosphorylation of DDR1 was consistently enabled by expression of Wnt-5a-HA protein in non-Wnt-5a-producing MCF-7 breast cancer cells. Activation of the Wnt/beta-catenin signalling pathway did not influence or mimic the Wnt-5a-mediated effect on DDR1 phosphorylation. These data demonstrate that Wnt-5a protein participates in regulation of adhesion to and migration through collagen and is also a co-factor necessary for collagen-induced activation of DDR1 receptors in mammary epithelial cells. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1121845
- author
- Jönsson, Marzieh and Andersson, Tommy LU
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Cell Science
- volume
- 114
- issue
- Pt 11
- pages
- 2043 - 2053
- publisher
- The Company of Biologists Ltd
- external identifiers
-
- pmid:11493640
- scopus:0034960540
- ISSN
- 0021-9533
- language
- English
- LU publication?
- yes
- id
- da181ab4-be14-4948-8e7b-71dd70cb0062 (old id 1121845)
- alternative location
- http://jcs.biologists.org/cgi/reprint/114/11/2043
- date added to LUP
- 2016-04-01 11:56:07
- date last changed
- 2022-02-18 07:30:26
@article{da181ab4-be14-4948-8e7b-71dd70cb0062,
abstract = {{The Wnt-5a gene encodes a secreted protein that controls several normal processes during embryogenesis and development of adult tissues by as yet unknown mechanisms. Endogenous expression of Wnt-5a mRNA is known to occur in both mouse and human mammary cell lines. To investigate the biological role of Wnt-5a in the human mammary epithelial cell line HB2, we used an antisense approach to repress endogenous expression of Wnt-5a protein. We also generated a cell population that constitutively overexpresses this protein. We found that overexpression of Wnt-5a protein enhanced cell-to-collagen binding and abolished hepatocyte growth factor-stimulated migration of HB2 transfectants through collagen matrices. Conversely, repression of Wnt-5a protein led to cell scattering, impaired cell-collagen interaction and enhanced cell motility. As we were searching for modified collagen receptors in antisense cells, we discovered that the collagen-binding discoidin domain receptor 1 (DDR1) failed to undergo phosphorylation. In reciprocal experiments, phosphorylation of DDR1 was consistently enabled by expression of Wnt-5a-HA protein in non-Wnt-5a-producing MCF-7 breast cancer cells. Activation of the Wnt/beta-catenin signalling pathway did not influence or mimic the Wnt-5a-mediated effect on DDR1 phosphorylation. These data demonstrate that Wnt-5a protein participates in regulation of adhesion to and migration through collagen and is also a co-factor necessary for collagen-induced activation of DDR1 receptors in mammary epithelial cells.}},
author = {{Jönsson, Marzieh and Andersson, Tommy}},
issn = {{0021-9533}},
language = {{eng}},
number = {{Pt 11}},
pages = {{2043--2053}},
publisher = {{The Company of Biologists Ltd}},
series = {{Journal of Cell Science}},
title = {{Repression of Wnt-5a impairs DDR1 phosphorylation and modifies adhesion and migration of mammary cells}},
url = {{http://jcs.biologists.org/cgi/reprint/114/11/2043}},
volume = {{114}},
year = {{2001}},
}