title: Surface expression of precursor N-cadherin promotes tumor cell invasion.
abstract: The expression of N-cadherin (NCAD) has been shown to correlate with increased tumor cell motility and metastasis. However, NCAD-mediated adhesion is a robust phenomenon and therefore seems to be inconsistent with the "release" from intercellular adhesion required for invasion. We show that in the most invasive melanoma and brain tumor cells, altered posttranslational processing results in abundant nonadhesive precursor N-cadherin (proNCAD) at the cell surface, although total NCAD levels remain constant. We demonstrate that aberrantly processed proNCAD promotes cell migration and invasion in vitro. Furthermore, in human tumor specimens, we find high levels of proNCAD as well, supporting an overall conclusion that proNCAD and mature NCAD coexist on these tumor cell surfaces and that it is the ratio between these functionally antagonistic moieties that directly correlates with invasion potential. Our work provides insight into what may be a widespread mechanism for invasion and metastasis and challenges the current dogma of the functional roles played by classic cadherins in tumor progression.
authors.affiliation: Brain Tumour Research Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Deborah
authors.initials: D
authors.lastname: Maret
authors.forename: Eugenia
authors.initials: E
authors.lastname: Gruzglin
authors.forename: Mohamad Seyed
authors.initials: MS
authors.lastname: Sadr
authors.forename: Vincent
authors.initials: V
authors.lastname: Siu
authors.forename: Weisong
authors.initials: W
authors.lastname: Shan
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Koch
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
authors.forename: Rolando F
authors.initials: RF
authors.lastname: Del Maestro
authors.forename: David R
authors.initials: DR
authors.lastname: Colman
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D045683:Furin / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering
chemical_list: D015820:Cadherins; D011498:Protein Precursors; D034741:RNA, Small Interfering; D045683:Furin