N-Cadherin Promotes Motility in Human Breast Cancer Cells Regardless of Their E-Cadherin Expression

Abstract

E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent, homotypic cell–cell adhesion and plays a role in maintaining the normal phenotype of epithelial cells. Decreased expression of E-cadherin has been correlated with increased invasiveness of breast cancer. In other systems, inappropriate expression of a nonepithelial cadherin, such as N-cadherin, by an epithelial cell has been shown to downregulate E-cadherin expression and to contribute to a scattered phenotype. In this study, we explored the possibility that expression of nonepithelial cadherins may be correlated with increased motility and invasion in breast cancer cells. We show that N-cadherin promotes motility and invasion; that decreased expression of E-cadherin does not necessarily correlate with motility or invasion; that N-cadherin expression correlates both with invasion and motility, and likely plays a direct role in promoting motility; that forced expression of E-cadherin in invasive, N-cadherin–positive cells does not reduce their motility or invasive capacity; that forced expression of N-cadherin in noninvasive, E-cadherin–positive cells produces an invasive cell, even though these cells continue to express high levels of E-cadherin; that N-cadherin–dependent motility may be mediated by FGF receptor signaling; and that cadherin-11 promotes epithelial cell motility in a manner similar to N-cadherin.

Cadherin switching and activation of p120 catenin signaling are mediators of gonadotropin-releasing hormone to promote tumor cell migration and invasion in ovarian cancer

“…Our finding that P-cadherin as a critical mediator of the invasive phenotype further supports the view that the incorrect expression of another adhesion molecule, rather than a decrease in E-cadherin, is associated with an increased invasive potential (Nieman et al, 1999;Feltes et al, 2002;Suyama et al, 2002;Maeda et al, 2006). Unlike E-cadherin, P-cadherin can promote motility and invasion in carcinoma cells.…”

“…Instead, GnRHa stimulated activation of the P-cadherin promoter (Figure 2b; Po0.05), suggesting a transcriptional mechanism of regulation. P-cadherin contributes to the invasive phenotype It has been suggested that expression of an inappropriate cadherin may directly contribute to the invasive phenotype (Nieman et al, 1999;Feltes et al, 2002;Suyama et al, 2002;Maeda et al, 2006). To test whether P-cadherin may promote migration/invasion, we stably transfected Caov-3 and OVCAR-3 cells with P-cadherin and analyzed their effects on cell migration/invasion.…”

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

“…We sought to study changes in the expression and localization of CRB3 (apical) and occludin (basolateral) as epithelial markers of EMT-associated processes, rather than the direct effect of E2 on the expression of these proteins. On the other hand, gradual increases of N-cadherin expression in these breast cancer cell lines were related to EMT-associated mechanisms, regardless of the E-cadherin expression [46], and could be used as stage markers during invasion processes. Furthermore, it has been reported that Ncadherin expression correlates with invasion and motility, plays a direct role in promoting motility, and is involved in EMT and cancer cell metastasis [47].…”

Overexpression of homeobox geneHOXD3 induces coordinate expression of metastasis-related genes in human lung cancer cells

“…N-cadhein is upregulated in highly invasive breast cancer cell lines that lack Ecadherin expression. 39 Further, exogenous expression of N-cadherin in breast cancer cells enhances motile, invasive and metastatic ability. 40 Human squamous carcinoma cells that express N-cadherin along with a decreased expression of E-and P-cadherin disrupt cell-cell adhesion and induce a scattered fibroblastic phenotype.…”