Lack of Cell Adhesion Protein Paves Way for Breast Cancer Development

A protein that is deficient in some types of breast tumors has been linked to the formation of desmosomes, complex protein structures that bind cells together into tissues and organs.

Desmosomes are molecular complexes of cell adhesion and linking proteins that attach cell surface adhesion proteins to intracellular keratin cytoskeletal filaments. The cell adhesion proteins of the desmosome, desmoglein and desmocollin, are members of the cadherin family of cell adhesion molecules. They are transmembrane proteins that bridge the space between adjacent epithelial cells by way of homophilic binding of their extracellular domains to other desmosomal cadherins on the adjacent cell. Both have five extracellular domains, and have calcium-binding motifs.

A protein called Perp (TP53 apoptosis effector) had been shown previously to have a role in stratified epithelial integrity and cell-cell adhesion by promoting desmosome assembly. In the current study, investigators at Stanford University (Palo Alto, CA, USA) sought to explain why mice genetically engineered to lack the gene for Perp production suffered from severe blistering of the epidermis and oral mucosa and how this type of inflammatory response was linked to formation of breast tumors.

They reported in the April 20, 2012, online edition of the journal Breast Cancer Research that Perp protein was expressed in the mammary epithelium, where it co-localized with desmosomes. Perp loss affected mammary epithelial homeostasis by causing the accumulation of inflammatory cells around mature mammary epithelium. Reduced Perp expression was detected in many human breast cancer cell lines compared to untransformed cells, and Perp-deficiency promoted the development of mouse mammary cancer.

Senior author Dr. Laura Attardi, associate professor of radiation oncology at Stanford University, said, “Perp deficiency caused defects in desmosomal protein expression in breast epithelial cells. At the same time, there was an enhanced inflammatory response in the breast tissue, and tumors tended to develop more quickly. We also found in the lab that breast cancer cells had abnormally low levels of Perp.”

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