title: Cadherin switch in tumor progression.
abstract: The loss of E-cadherin expression or function in epithelial carcinomas has long been thought as a primary reason for disruption of tight epithelial cell-cell contacts and release of invasive tumor cells from the primary tumor. Indeed, E-cadherin serves as a widely acting suppressor of invasion and growth of epithelial cancers, and its functional elimination represents a key step in the acquisition of the invasive phenotype for many tumors. Recent evidence indicates, however, that in addition to the loss of the "invasion-suppressor" E-cadherin, another adhesion molecule, N-cadherin, becomes upregulated in invasive tumor cell lines. N-cadherin was shown to be present in the most invasive and dedifferentiated breast cancer cell lines, and its exogenous expression in tumor cells induces a scattered morphology and heightened motility, invasion, and metastasis. N-cadherin cooperates with the FGF receptor, resulting in signals that lead to the up-modulation of MMP-9 and, hence, cellular invasion. In addition to a signaling function in metastasis, N-cadherin probably also supports the systemic dissemination of tumor cells by enabling circulating tumor cells to associate with the stroma and the endothelium at distant sites. Here, we summarize the various aspects of the E- to N-cadherin switching in epithelial carcinomas and its potential impact on metastatic progression.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. rhazan@aecom.yu.edu
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Hazan
authors.forename: Rui
authors.initials: R
authors.lastname: Qiao
authors.forename: Rinat
authors.initials: R
authors.lastname: Keren
authors.forename: Ines
authors.initials: I
authors.lastname: Badano
authors.forename: Kimita
authors.initials: K
authors.lastname: Suyama
mesh_terms: D015820:Cadherins / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000503:physiopathology*
chemical_list: D015820:Cadherins