Abrogation of Junctional Adhesion Molecule-A Expression Induces Cell Apoptosis and Reduces Breast Cancer Progression
Open Access
- 17 June 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (6), e21242
- https://doi.org/10.1371/journal.pone.0021242
Abstract
Intercellular junctions promote homotypic cell to cell adhesion and transfer intracellular signals which control cell growth and apoptosis. Junctional adhesion molecule-A (JAM-A) is a transmembrane immunoglobulin located at tight junctions of normal epithelial cells of mammary ducts and glands. In the present paper we show that JAM-A acts as a survival factor for mammary carcinoma cells. JAM-A null mice expressing Polyoma Middle T under MMTV promoter develop significantly smaller mammary tumors than JAM-A positive mice. Angiogenesis and inflammatory or immune infiltrate were not statistically modified in absence of JAM-A but tumor cell apoptosis was significantly increased. Tumor cells isolated from JAM-A null mice or 4T1 cells incubated with JAM-A blocking antibodies showed reduced growth and increased apoptosis which paralleled altered junctional architecture and adhesive function. In a breast cancer clinical data set, tissue microarray data show that JAM-A expression correlates with poor prognosis. Gene expression analysis of mouse tumor samples showed a correlation between genes enriched in human G3 tumors and genes over expressed in JAM-A +/+ mammary tumors. Conversely, genes enriched in G1 human tumors correlate with genes overexpressed in JAM-A−/− tumors. We conclude that down regulation of JAM-A reduces tumor aggressive behavior by increasing cell susceptibility to apoptosis. JAM-A may be considered a negative prognostic factor and a potential therapeutic target.Keywords
This publication has 29 references indexed in Scilit:
- Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPaseBreast Cancer Research, 2011
- miR-145-dependent targeting of Junctional Adhesion Molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasivenessOncogene, 2010
- Structural determinants of Junctional Adhesion Molecule A (JAM-A) function and mechanisms of intracellular signalingCurrent Opinion in Cell Biology, 2009
- A Distinct Macrophage Population Mediates Metastatic Breast Cancer Cell Extravasation, Establishment and GrowthPLOS ONE, 2009
- Alterations of ubiquitin ligases in human cancer and their association with the natural history of the tumorOncogene, 2009
- Downregulation of junctional adhesion molecule-A is involved in the progression of clear cell renal cell carcinomaBiochemical and Biophysical Research Communications, 2009
- JAM-A promotes neutrophil chemotaxis by controlling integrin internalization and recyclingJournal of Cell Science, 2009
- JAM-A regulates permeability and inflammation in the intestine in vivoThe Journal of Experimental Medicine, 2007
- Getting to the site of inflammation: the leukocyte adhesion cascade updatedNature Reviews Immunology, 2007
- The mouse mammary carcinoma 4T1: characterization of the cellular landscape of primary tumours and metastatic tumour fociInternational Journal of Experimental Pathology, 2007