Disruption of E-Cadherin Pattern in Uterine and Mammary Tumours

Abstract

E-cadherin (E-cadh), a member of the classic cadherins superfamily, plays an important role in epithelial cell-to-cell adhesion, encompassing the dynamic interactions between adjacent cells including the control of morphogenesis, maintenance of cell polarity and tissue architecture. Cadherins comprise a large family of cell surface glycoproteins, presenting unique extracellular regions domains known as the cadherin motifs or domains, which fold like immunoglobulin domains. They mediate strong Ca2+-dependent homophilic interactions between neighbouring epithelial cells, resulting in the formation of cell adhesion "zippers." E-cadh cytoplasmic tail links to catenins and, thereby to the actin cytoskeleton and signalling proteins to form a cell-cell signalling centre: it regulates several intracellular signal transduction pathways, including Wnt/-catenin, PI3K/Akt, Rho GTPase, and NF-KB signalling. E-cadh plays a crucial role in the barrier formation of polarized epithelial cell layers at the interfaces contacting with the external environment, namely the uterus and the mammary gland. The maintenance of these barriers could be considered as a prime immunologic function of E-cadh, compartmentalizing potentially harmful agents away from the underlying tissue. Disruption of classical cadherin expression has been related to the occurrence of diseases driving disturbances in tissue architecture, such as inflammation and cancer. In cancer, loss of E-cadh expression/function increases cell proliferation, cell migration, and disruption of epithelial cell homeostasis, driving cell dissociation and scattering. Alterations of E-cadh expression have also been reported during particular moments of the female reproductive physiology, namely throughout the oestrous cycle or during the embryo-maternal interaction at embryo implantation (early pregnancy). Several studies have shown the downregulation of E-cadh in malignant epithelial tumours, which has been associated with loss of cell differentiation, epithelial to mesenchymal transition (EMT) and invasion. Data also suggest that loss of E-cadh may be associated with malignant progression, metastasis, and reduced survival in multiple cancer patients. In this chapter, we review and discuss the role of E-cadh in the uterine and mammary gland homeostasis and describe disruptive patterns of E-cadh expression in neoplastic conditions of the uterus and mammary glands in human and domestic dogs and cats.