Abrogation of junctional adhesion molecule-A expression induces cell apoptosis and reduces breast cancer progression

Masato Murakami, Costanza Giampietro, Monica Giannotta, Monica Corada, Ilaria Torselli, Fabrizio Orsenigo, Andrea Cocito, Giovanni d'Ario, Giovanni Mazzarol, Stefano Confalonieri, Pier Paolo Fiore, Elisabetta Dejana

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere21242
JournalPLoS One
Volume6
Issue number6
DOIs
Publication statusPublished - 2011

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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  • Cite this

    Murakami, M., Giampietro, C., Giannotta, M., Corada, M., Torselli, I., Orsenigo, F., Cocito, A., d'Ario, G., Mazzarol, G., Confalonieri, S., Fiore, P. P., & Dejana, E. (2011). Abrogation of junctional adhesion molecule-A expression induces cell apoptosis and reduces breast cancer progression. PLoS One, 6(6), [e21242]. https://doi.org/10.1371/journal.pone.0021242