Desmosomes in breast cancer

Desmosomes are multifaceted intracellular junctions that participate in cell adhesion and maintenance of normal tissue structure. Desmosomes connect epithelial cells, myoepithelial cells, and the two cell types to each other. Despite the strong adhesion that desmosomes provide, the role of desmosomes in breast cancer metastasis is enigmatic. The loss of desmoplakin in breast cancers correlates with amplified proliferation and increased tumor size, suggesting that desmosomal proteins might be important in suppressing breast cancer progression. Desmoplakin levels are generally lower in metastases compared to primary tumors (67). Downregulation of DSC3 in breast cancer was first reported by Klus (68). Desmocollin 3 (DSC3), a p53 responsive gene, is expressed in normal breast while its expression is downregulated in both primary breast tumors and breast tumor cell lines (69). Decreased expression of DSC3 is partly due to cytosine hypermethylation and histone deacetyla-tion (70). Therefore, the loss of DSC3 expression in the cell lines appears to be due to both epigenetic and genetic changes. Hence, loss of desmo-somes might play a role in progression of tumor cells from the well to poorly differentiated phenotype. Clearly, the role of desmosomes in breast cancer is an area that needs more attention.

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