Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mol Cell Biol. 2002 Feb;22(4):1184-93.

Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors.

Author information

  • 1Max Delbrueck Center for Molecular Medicine, D-13092 Berlin, Germany.

Abstract

Activation of Wnt signaling through beta-catenin/TCF complexes is a key event in the development of various tumors, in particular colorectal and liver tumors. Wnt signaling is controlled by the negative regulator conductin/axin2/axil, which induces degradation of beta-catenin by functional interaction with the tumor suppressor APC and the serine/threonine kinase GSK3beta. Here we show that conductin is upregulated in human tumors that are induced by beta-catenin/Wnt signaling, i.e., high levels of conductin protein and mRNA were found in colorectal and liver tumors but not in the corresponding normal tissues. In various other tumor types, conductin levels did not differ between tumor and normal tissue. Upregulation of conductin was also observed in the APC-deficient intestinal tumors of Min mice. Inhibition of Wnt signaling by a dominant-negative mutant of TCF downregulated conductin but not the related protein, axin, in DLD1 colorectal tumor cells. Conversely, activation of Wnt signaling by Wnt-1 or dishevelled increased conductin levels in MDA MB 231 and Neuro2A cells, respectively. In time course experiments, stabilization of beta-catenin preceded the upregulation of conductin by Wnt-1. These results demonstrate that conductin is a target of the Wnt signaling pathway. Upregulation of conductin may constitute a negative feedback loop that controls Wnt signaling activity.

PMID:
11809809
[PubMed - indexed for MEDLINE]
PMCID:
PMC134640
Free PMC Article

Images from this publication.See all images (6)Free text

FIG. 1.
FIG. 2.
FIG. 3.
FIG.4.
FIG. 5.
FIG. 6.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk