JAM-A expression positively correlates with poor prognosis in breast cancer patients
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1476295
- author
- 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.
- organization
- publishing date
- 2009
- 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
- 2024-01-07 22:48:46
@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}}, keywords = {{junctional adhesion molecule-A; breast cancer; tight junction; migration}}, 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}}, }