Expression and signaling activity of Wnt-5a/discoidin domain receptor-1 and Syk plays distinct but decisive roles in breast cancer patient survival
Sand-Dejmek, Janna LU ; Leandersson, Karin LU
; Manjer, Jonas
LU
; Bjartell, Anders
LU
; Emdin, S O
; Vogel, WF
; Landberg, Göran
LU
and Andersson, Tommy
LU
(2005)
In Clinical Cancer Research
11(2).
p.520-528
- Abstract
- Purpose: The loss of Wnt-5a, a G-protein-coupled receptor ligand, or Syk, an intracellular kinase, has in separate studies been associated with poor prognosis of breast cancer patients. Both proteins are involved in cell adhesion, a key event in epithelial cancer metastasis. Here, we have investigated whether Syk is part of the Wnt-5a/discoidin domain receptor-1 (DDR1) signaling pathway and if a signaling interaction of these proteins is important for breast cancer-specific survival. Experimental Design: The signaling interactions between Wnt-5a/DDR1 and Syk were addressed in mammary cell lines. Their mRNA and protein levels and the respective clinical correlates were investigated in 94 cases of primary breast cancer. Results: The... (More)
- Purpose: The loss of Wnt-5a, a G-protein-coupled receptor ligand, or Syk, an intracellular kinase, has in separate studies been associated with poor prognosis of breast cancer patients. Both proteins are involved in cell adhesion, a key event in epithelial cancer metastasis. Here, we have investigated whether Syk is part of the Wnt-5a/discoidin domain receptor-1 (DDR1) signaling pathway and if a signaling interaction of these proteins is important for breast cancer-specific survival. Experimental Design: The signaling interactions between Wnt-5a/DDR1 and Syk were addressed in mammary cell lines. Their mRNA and protein levels and the respective clinical correlates were investigated in 94 cases of primary breast cancer. Results: The expression of Wnt-5a and Syk correlated in four of five tumor cell lines. However, despite a constitutive association between Syk and the Wnt-5a-dependent adhesion receptor DDR1, we found no evidence of a Wnt-5a/DDR1-mediated activation of Syk. Instead, beta(1) integrins initiate the adhesion-induced activation of Syk. In tumors from breast cancer patients, the protein expression of Wnt-5a and Syk were differently regulated at the translational and transcriptional level, respectively. Analysis of breast cancer-specific survival revealed that the presence of Wnt-5a and Syk in primary tumors has good predictive value for a favorable outcome. Intriguingly, a simultaneous loss of both proteins did not reduce survival more than loss of either. Conclusions: Despite the difference in regulation of Wnt-5a and Syk protein expression and their lack of signaling interaction, our clinical data indicate that a favorable prognosis in breast cancer requires the expression and signaling activity of both. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/255369
- author
- Sand-Dejmek, Janna
LU
; Leandersson, Karin
LU
; Manjer, Jonas
LU
; Bjartell, Anders
LU
; Emdin, S O
; Vogel, WF
; Landberg, Göran
LU
and Andersson, Tommy
LU
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Clinical Cancer Research
- volume
- 11
- issue
- 2
- pages
- 520 - 528
- publisher
- American Association for Cancer Research
- external identifiers
-
- wos:000226438000015
- pmid:15701836
- scopus:18244387242
- ISSN
- 1078-0432
- language
- English
- LU publication?
- yes
- id
- 56ba11ff-8338-4c21-a65c-8ba5825d0f6d (old id 255369)
- alternative location
- http://clincancerres.aacrjournals.org/cgi/content/abstract/11/2/520
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15701836&dopt=Abstract
- date added to LUP
- 2016-04-01 12:23:21
- date last changed
- 2022-07-30 02:00:53
@article{56ba11ff-8338-4c21-a65c-8ba5825d0f6d,
abstract = {{Purpose: The loss of Wnt-5a, a G-protein-coupled receptor ligand, or Syk, an intracellular kinase, has in separate studies been associated with poor prognosis of breast cancer patients. Both proteins are involved in cell adhesion, a key event in epithelial cancer metastasis. Here, we have investigated whether Syk is part of the Wnt-5a/discoidin domain receptor-1 (DDR1) signaling pathway and if a signaling interaction of these proteins is important for breast cancer-specific survival. Experimental Design: The signaling interactions between Wnt-5a/DDR1 and Syk were addressed in mammary cell lines. Their mRNA and protein levels and the respective clinical correlates were investigated in 94 cases of primary breast cancer. Results: The expression of Wnt-5a and Syk correlated in four of five tumor cell lines. However, despite a constitutive association between Syk and the Wnt-5a-dependent adhesion receptor DDR1, we found no evidence of a Wnt-5a/DDR1-mediated activation of Syk. Instead, beta(1) integrins initiate the adhesion-induced activation of Syk. In tumors from breast cancer patients, the protein expression of Wnt-5a and Syk were differently regulated at the translational and transcriptional level, respectively. Analysis of breast cancer-specific survival revealed that the presence of Wnt-5a and Syk in primary tumors has good predictive value for a favorable outcome. Intriguingly, a simultaneous loss of both proteins did not reduce survival more than loss of either. Conclusions: Despite the difference in regulation of Wnt-5a and Syk protein expression and their lack of signaling interaction, our clinical data indicate that a favorable prognosis in breast cancer requires the expression and signaling activity of both.}},
author = {{Sand-Dejmek, Janna and Leandersson, Karin and Manjer, Jonas and Bjartell, Anders and Emdin, S O and Vogel, WF and Landberg, Göran and Andersson, Tommy}},
issn = {{1078-0432}},
language = {{eng}},
number = {{2}},
pages = {{520--528}},
publisher = {{American Association for Cancer Research}},
series = {{Clinical Cancer Research}},
title = {{Expression and signaling activity of Wnt-5a/discoidin domain receptor-1 and Syk plays distinct but decisive roles in breast cancer patient survival}},
url = {{http://clincancerres.aacrjournals.org/cgi/content/abstract/11/2/520}},
volume = {{11}},
year = {{2005}},
}