Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell Biol Int. 2002;26(5):463-76.

Direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of EMT.

Author information

  • 1Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

Epithelial-mesenchymal transformation (EMT) is an important process in development that is characterized by loss of E-cadherin, beta-catenin relocalization, and acquisition of elongated cell shape and ability to invade ECM. beta-catenin has been shown to activate LEF-1 transcription during EMT induced in vitro by c-Fos. Here, we ask whether or not LEF-1 directly introduced into epithelial cells in an adenovirus construct can induce EMT. In normal epithelial cell lines, such as HCE and MDCK cells, that contain functional APC, nuclear beta-catenin induced by exogenous LEF-1 is rapidly exported and EMT is not induced. Leptomycin-B blocks beta-catenin nuclear export, but no EMT occurs due to toxicity. Addition of Wnt-1 to normal epithelial cell lines stabilizes cytoplasmic beta-catenin that LEF-1 then transports to nuclei, causing a small amount of EMT. Our experiments demonstrated, however, that overexpressed LEF-1 upregulates nuclear beta-catenin and promotes dramatic EMT in DLD-1 epithelial tumors that retain nuclear beta-catenin. This EMT is reversible if the LEF-1 virus is removed. Thus, our results demonstrate that LEF-1 can induce EMT directly when its transcription activity is activated by stable nuclear beta-catenin. Normal adult epithelial cells appear to use APC to keep beta-catenin out of the nucleus, thereby avoiding pathologies such as metastases due to LEF/beta-catenin-induced EMT.

Copyright 2002 Elsevier Science Ltd. All rights reserved.

PMID:
12095232
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Portland Press
    Loading ...
    Write to the Help Desk