N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression.
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.
Nieman
M T
MT
Department of Biology, University of Toledo, Toledo, Ohio 43606, USA.
Prudoff
R S
RS
Johnson
K R
KR
Wheelock
M J
MJ
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D048429:Cell Size; D018920:Coculture Techniques; D003512:Cyclohexanones / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000235:genetics*; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D015398:Signal Transduction; D015534:Trans-Activators; D014162:Transfection; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003512:Cyclohexanones; D003598:Cytoskeletal Proteins; D017468:Receptors, Fibroblast Growth Factor; D015534:Trans-Activators; D051176:beta Catenin; C086960:osteoblast cadherin; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D008071:Lipoprotein Lipase