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JAM-A expression positively correlates with poor prognosis in breast cancer patients

McSherry, Elaine A. ; McGee, Sharon F. ; Jirström, Karin LU ; Doyle, Emma M. ; Brennan, Donal J. ; Landberg, Göran LU ; Dervan, Peter A. ; Hopkins, Ann M. and Gallagher, William M. (2009) In International Journal of Cancer 125(6). p.1343-1351
Abstract
The cell-cell adhesion protein junctional adhesion molecule-A (JAM-A) influences; epithelial cell morphology and migration. As migration is required for tumor cell invasion and metastasis, we sought to elucidate the role of JAM-A in invasive breast cancer. A breast cancer tissue microarray was analyzed for JAM-A protein expression, in parallel with analysis of JAM-A gene expression data from a breast cancer clinical dataset. Our data demonstrate a novel association between JAM-A gene and protein upregulation and poor prognosis in breast cancer. To mechanistically dissect this process, we used lentiviral technology to stably knock down JAM-A gene expression by shRNA in MCF7 breast cancer cells, which express high-endogenous levels of JAM-A.... (More)
The cell-cell adhesion protein junctional adhesion molecule-A (JAM-A) influences; epithelial cell morphology and migration. As migration is required for tumor cell invasion and metastasis, we sought to elucidate the role of JAM-A in invasive breast cancer. A breast cancer tissue microarray was analyzed for JAM-A protein expression, in parallel with analysis of JAM-A gene expression data from a breast cancer clinical dataset. Our data demonstrate a novel association between JAM-A gene and protein upregulation and poor prognosis in breast cancer. To mechanistically dissect this process, we used lentiviral technology to stably knock down JAM-A gene expression by shRNA in MCF7 breast cancer cells, which express high-endogenous levels of JAM-A. We also antagonized JAM-A function in wild-type MCF7 cells using an inhibitory antibody that blocks JAM-A dimerization. Knockdown or functional antagonism of JAM-A decreased breast cancer cell migration in scratch-wound assays. Reductions in beta 1-integrin protein levels were observed after JAM-A-knockdown in MCF7 cells, suggesting a mechanism for reduced motility after loss of JAM-A. Consistent with this hypothesis, tissue microarray analysis of beta 1-integrin protein expression in invasive breast cancer tissues revealed a trend toward high beta 1-integrin protein levels being indicative of poor prognosis. Twenty-two percent of patients were observed to coexpress high levels of JAM-A and beta 1-integrin protein, and MDA-MB-231 breast cells stably overexpressing JAM-A showed an increase in beta 1-integrin protein expression. Our results are consistent with a previously unreported role for JAM-A overexpression as a possible mechanism contributing to progression in primary breast cancer; and a potential therapeutic target. (C) 2009 UICC (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
junctional adhesion molecule-A, breast cancer, tight junction, migration
in
International Journal of Cancer
volume
125
issue
6
pages
1343 - 1351
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000269392700012
  • scopus:68249147448
ISSN
0020-7136
DOI
10.1002/ijc.24498
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology (Malmö) (013031000), Pathology, (Lund) (013030000)
id
76499f35-18a4-42c8-90a9-d6e01564652c (old id 1476295)
date added to LUP
2016-04-01 11:51:19
date last changed
2021-10-06 04:23:25
@article{76499f35-18a4-42c8-90a9-d6e01564652c,
  abstract     = {The cell-cell adhesion protein junctional adhesion molecule-A (JAM-A) influences; epithelial cell morphology and migration. As migration is required for tumor cell invasion and metastasis, we sought to elucidate the role of JAM-A in invasive breast cancer. A breast cancer tissue microarray was analyzed for JAM-A protein expression, in parallel with analysis of JAM-A gene expression data from a breast cancer clinical dataset. Our data demonstrate a novel association between JAM-A gene and protein upregulation and poor prognosis in breast cancer. To mechanistically dissect this process, we used lentiviral technology to stably knock down JAM-A gene expression by shRNA in MCF7 breast cancer cells, which express high-endogenous levels of JAM-A. We also antagonized JAM-A function in wild-type MCF7 cells using an inhibitory antibody that blocks JAM-A dimerization. Knockdown or functional antagonism of JAM-A decreased breast cancer cell migration in scratch-wound assays. Reductions in beta 1-integrin protein levels were observed after JAM-A-knockdown in MCF7 cells, suggesting a mechanism for reduced motility after loss of JAM-A. Consistent with this hypothesis, tissue microarray analysis of beta 1-integrin protein expression in invasive breast cancer tissues revealed a trend toward high beta 1-integrin protein levels being indicative of poor prognosis. Twenty-two percent of patients were observed to coexpress high levels of JAM-A and beta 1-integrin protein, and MDA-MB-231 breast cells stably overexpressing JAM-A showed an increase in beta 1-integrin protein expression. Our results are consistent with a previously unreported role for JAM-A overexpression as a possible mechanism contributing to progression in primary breast cancer; and a potential therapeutic target. (C) 2009 UICC},
  author       = {McSherry, Elaine A. and McGee, Sharon F. and Jirström, Karin and Doyle, Emma M. and Brennan, Donal J. and Landberg, Göran and Dervan, Peter A. and Hopkins, Ann M. and Gallagher, William M.},
  issn         = {0020-7136},
  language     = {eng},
  number       = {6},
  pages        = {1343--1351},
  publisher    = {John Wiley & Sons Inc.},
  series       = {International Journal of Cancer},
  title        = {JAM-A expression positively correlates with poor prognosis in breast cancer patients},
  url          = {http://dx.doi.org/10.1002/ijc.24498},
  doi          = {10.1002/ijc.24498},
  volume       = {125},
  year         = {2009},
}