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.

journal_name

Neoplasia

authors

Maret D,Gruzglin E,Sadr MS,Siu V,Shan W,Koch AW,Seidah NG,Del Maestro RF,Colman DR

doi

10.1593/neo.10954

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

1066-80

issue

12

eissn

1522-8002

issn

1476-5586

journal_volume

12

pub_type

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