Cadherin switching

Abstract

occurs during normal developmental processes to allow cell types to segregate from one another. Tumor cells often recapitulate this activity and the result is an aggressive tumor cell that gains the ability to leave the site of the tumor and metastasize. At present, we understand some of the mechanisms that promote cadherin switching and some of the pathways downstream of this process that influence cell behavior. Specific cadherin family members influence growthfactor-receptor signaling and Rho GTPases to promote cell motility and invasion. In addition, p120-catenin probably plays multiple roles in cadherin switching, regulating Rho GTPases and stabilizing cadherins. Journal of Cell Science 728cadherin expression has been shown to promote motility and invasion (Hazan et al., 2000; Islam et al., 1996;Nieman et al., 1999). This loss of E-cadherin expression and gain of N-cadherin expression is reminiscent of the cadherin switching that is seen during normal embryonic development and probably underpins many of the phenotypic changes that occur in the participating cells (reviewed in Cavallaro et al., 2002; Christofori, 2003; Gerhart et al., 2004).The term cadherin switching usually refers to a switch from expression of E-cadherin to expression of N-cadherin, but also includes situations in which E-cadherin expression levels do not change significantly but the cells turn on (or increase) expression of N-cadherin. It also includes examples in which other cadherins replace or are co-expressed with E-cadherin, including R-cadherin, cadherin 11, T-cadherin and even P-cadherin, and the expression of the 'inappropriate cadherin' might alter the behavior of the tumor cells (Derycke and Bracke, 2004;Nakajima et al., 2004;Paredes et al., 2005;Patel, I. et al., 2003;Riou et al., 2006;Stefansson et al., 2004;Taniuchi et al., 2005;Tomita et al., 2000). It has even been reported that E-cadherin can influence tumorigenesis in tissues that do not normally express this cadherin. For example, ovarian surface epithelium normally expresses N-cadherin. However, during progression to the neoplastic state, the cells show decreased N-cadherin expression and increased E-cadherin and Pcadherin expression; the E-cadherin might play a role in the initiation of the aberrant differentiation that characterizes ovarian carcinogenesis (Patel, I. et al., 2003;Wong et al., 1999;Wu et al., 2007). Table 1 presents examples of cadherin switching that have been reported during normal developmental processes and during tumorigenesis.One role of cadherin switching is to allow a select population of cells to separate from their neighbors -for example, during processes such as gastrulation, epiblast cell ingression through the primitive streak and neural crest emigration from the neural tube (Edelman et al., 1983; Hatta and Takeichi, 1986;Takeichi, 1988;Takeichi et al., 2000). It is well known that cells expressing different cadherins segregate from one another in in vitro aggregation assays (Nose et al., 1988;Steinberg and Takeichi, 1994) and it is easy...

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

“…Alteration in cell adhesion is a hallmark feature of metastasis (Wheelock et al, 2008). Earlier studies have documented the switching of cadherin profiles during ovarian tumor progression (Patel et al, 2003).…”

“…Cadherins are a family of transmembrane glycoproteins that mediate Ca 2 þ -dependent homophilic cell-cell adhesion. Cadherin subtype switching in which other cadherins replace or are co-expressed with E-cadherin during embryogenesis has important functional roles in cell segregation (Wheelock et al, 2008). Tumor cells often recapitulate this activity during cancer progression in which tumor cells acquire the capacity to migrate, invade, and metastasize.…”

Timing and kinetics of E‐ to N‐cadherin switch during neurulation in the avian embryo

“…Consistent with this, biophysical studies demonstrated that E-cadherin mediates stronger bonds at the molecular level than any other cadherins (Dufour et al, 1999;Chu et al, 2006;Panorchan et al, 2006). Moreover, although E-cadherin and N-cadherin may transiently coexist in certain cells, they are generally mutually exclusive, and studies on epithelial cell lines or in mouse and Xenopus embryos in which E-and N-cadherins have been interchanged clearly indicate that they can only partially substitute each other (Luo et al, 2001;Kan et al, 2007;Wheelock et al, 2008;Nandadasa et al, 2009;Libusova et al, 2010).…”

“…In particular, the switch between E-and N-cadherin has been found to play a key role in early morphogenesis and in pathological situations, by promoting the process of epithelium-to-mesenchyme transition (EMT; Wheelock et al, 2008;Thiery et al, 2009). During gastrulation, for example, N-cadherin is up-regulated at the expense of E-cadherin on the surface of nascent mesodermal cells ingressing from the superficial ectoderm into the primitive streak (Ohta et al, 2007;Nakaya et al, 2008;Hardy et al, 2011).…”

The impact of adhesion on cellular invasion processes in cancer and development

“…see Christofori 2003;Cavallaro & Christofori 2004;Yilmaz & Christofori 2009). Recent focus has been paid to a "cadherin switch" (Wheelock et al 2008), in which loss of E-cadherin is further accompanied by gain in the mesenchymal CAM N-cadherin, and the cell subsequently loses its affinity for its epithelial neighbours.…”