The role of E-cadherin - 160C/A polymorphism in breast cancer

Abstract

Open Life Sci. 2016; 11: 110-115 invasion and metastases. These characteristics are results of genetic deregulation. Accumulation of genetic mutations results in increasingly aggressive phenotypes [5]. E-cadherin in Breast Cancer Structure and Functions of E-CadherinThe CDH1 gene is located on human chromosome 16q22.1 and encodes for the E-cadherin protein [6]. The E-cadherin glycoprotein is composed of three major structural domains: a single transmembrane domain, connected with a cytoplasmic domain, and an extracellular domain comprising five tandemly repeated domains called EC1-EC5, which are exclusive to cadherins [7]. The extracellular domain of E-cadherin is essential for cell to cell adhesion, as well as for the correct folding and homo/hetero dimerisation of the proteins. The cytoplasmic domain of E-cadherin interacts with the catenins (α-, β-, γ-and p120 catenin) anchored to the actin cytoskeleton, establishing cadherin-catenin complexes [8]. Conformation of E-cadherin is only stable upon Ca 2+ binding to its highly conserved, negatively charged extracellular motifs [9]. Its stabilization at the cell membrane and accurate function occur by association to cytoplasmic p120-catenin [10]. E-cadherin forms adherens junction with its binding partner β-catenin and actin filaments. This complex is critical to inhibit individual epithelial cell motility and to provide homeostatic tissue architecture [11,12] (Figure 1). Signaling Pathways Regulated by E-CadherinIn addition to its role in cell to cell adhesion, E-cadherin is involved in a number of signaling pathways in carcinogenesis [13]. For the Wnt/β-catenin pathway, free β-catenins may accumulate in the cytoplasm attributed Abstract: Breast cancer is the most prevalent cancer in women worldwide. Numerous studies have suggested that the E-cadherin adhesion system is dysregulated in cancer cells. These impaired functions of E-cadherin contribute to releasing cancer cells from the primary lesion to cell dedifferentiation. Some studies have shown that polymorphism may affect E-cadherin expression, and then play a role in susceptibility to breast cancer. However, the results remained controversial. In this short review, we summarize the functions of E-cadherin and the signaling pathways it regulates, and assess the association between CDH1 polymorphisms and breast cancer susceptibility. This study suggests that genetic variation in CDH1 and -160C/A polymorphism may have an association with breast cancer risk. The assessment of CDH1 polymorphisms may be used for the identification of patients suitable for anti-CDH1 therapy.

Potent Suppression of Prostate Cancer Cell Growth and Eradication of Cancer Stem Cells by CD44-targeted Nanoliposome-quercetin Nanoparticles

“…In tumor cells where E-cadherin expression is lost, β-catenins, essential in mediating Wnt signaling, accumulate in high levels within the cytoplasm and translocate to the cell nucleus. Once in the nucleus, they bind to members of the transcription factor/lymphoid enhancer-binding factor 1 family, thereby contributing to tumor progression by activating Wnt target genes, like CD44, c-Myc and MMP-9 [ 48 ]. In this context, the noteworthy upregulation of E-cadherin observed in cells treated with LP-Quer-HA is of significance.…”

Implications of nestin in breast cancer pathogenesis (Review)

“…EMT is a dynamic process that appears to facilitate tumour metastasis by switching the cell phenotype from epithelial to mesenchymal (122,123). Furthermore, nestin silencing significantly upregulated the expression of proteins involved in the inhibition of the Wnt/β-catenin pathway, which is crucial for the regulation of the proliferation and tumorigenicity of stem cells (124)(125)(126)(127). In addition, the inhibition of the Wnt/β-catenin pathway in nestin high CSCs significantly limited their tumorigenicity.…”