JAM-A expression positively correlates with poor prognosis in breast cancer patients.
Elaine A. McSherry
Sharon F. McGee
Karin Jirstrom
Emma M. Doyle
Donal J. Brennan
Goran Landberg
Peter A. Dervan
Ann M. Hopkins
William M Gallagher
10779/rcsi.10800095.v1
https://repository.rcsi.com/articles/journal_contribution/JAM-A_expression_positively_correlates_with_poor_prognosis_in_breast_cancer_patients_/10800095
<p>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 beta1-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 beta1-integrin protein expression in invasive breast cancer tissues revealed a trend toward high beta1-integrin protein levels being indicative of poor prognosis. Twenty-two percent of patients were observed to coexpress high levels of JAM-A and beta1-integrin protein, and MDA-MB-231 breast cells stably overexpressing JAM-A showed an increase in beta1-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.</p>
2019-11-22 17:29:06
Adenocarcinoma
Mucinous
Adult
Aged
80 and over
Antigens
CD29
Blotting
Western
Breast Neoplasms
Carcinoma
Medullary
Cell Adhesion
Cell Adhesion Molecules
Cell Movement
Cell Proliferation
Female
Fluorescent Antibody Technique
Gene Expression Profiling
Gene Expression Regulation
Neoplastic
Humans
Immunoenzyme Techniques
Immunoglobulins
Middle Aged
Neoplasm Invasiveness
Oligonucleotide Array Sequence Analysis
Prognosis
RNA
Messenger
Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Survival Rate
Tissue Array Analysis
Tumor Markers
Biological
Wound Healing
Surgery