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PMID: 15084607 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Wnt11 signaling promotes proliferation, transformation, and migration of IEC6 intestinal epithelial cells.

The Journal of biological chemistry ·Vol. 279 ·No. 25 ·2004-06-18 ·Pages 26707-15

Ouko L, Ziegler TR, Gu LH, Eisenberg LM, Yang VW

Abstract

Wnts are morphogens with well recognized functions during embryogenesis. Aberrant Wnt signaling has been demonstrated to be important in colorectal carcinogenesis. However, the role of Wnt in regulating normal intestinal epithelial cell proliferation is not well established. Here we determine that Wnt11 is expressed throughout the mouse intestinal tract including the epithelial cells. Conditioned media from Wnt11-secreting cells stimulated proliferation and migration of IEC6 intestinal epithelial cells. Co-culture of Wnt11-secreting cells with IEC6 cells resulted in morphological transformation of the latter as evidenced by the formation of foci, a condition also accomplished by stable transfection of IEC6 with a Wnt11-expressing construct. Treatment of IEC6 cells with Wnt11 conditioned media failed to induce nuclear translocation of beta-catenin but led to increased activities of protein kinase C and Ca(2+)/calmodulin-dependent protein kinase II. Inhibition of protein kinase C resulted in a decreased ability of Wnt11 to induce foci formation in IEC6 cells. Finally, E-cadherin was redistributed in Wnt11-treated IEC6 cells, resulting in diminished E-cadherin-mediated cell-cell contact. We conclude that Wnt11 stimulates proliferation, migration, cytoskeletal rearrangement, and contact-independent growth of IEC6 cells by a beta-catenin-independent mechanism. These findings may help understand the molecular mechanisms that regulate proliferation and migration of intestinal epithelial cells.

MeSH Terms
Active Transport, Cell Nucleus Animals Blotting, Northern Blotting, Western Caco-2 Cells Cell Differentiation Cell Division Cell Line Cell Line, Tumor Cell Movement Cell Transformation, Neoplastic Coculture Techniques Culture Media, Conditioned/pharmacology Cytoskeletal Proteins/metabolism Cytoskeleton/metabolism Glycoproteins/metabolism,physiology Humans Immunohistochemistry Intestinal Mucosa/cytology Luciferases/metabolism Microscopy, Fluorescence Protein Kinase C/metabolism Rats Signal Transduction Time Factors Tissue Distribution Trans-Activators/metabolism Transfection Wnt Proteins beta Catenin
Chemicals
CTNNB1 protein, human Ctnnb1 protein, rat Culture Media, Conditioned Cytoskeletal Proteins Glycoproteins Trans-Activators Wnt Proteins beta Catenin Luciferases Protein Kinase C
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ouko Lillian
Divisions of Digestive Diseases and Endocrinology, Department of Medicine, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Ziegler Thomas R
Gu Li H
Eisenberg Leonard M
Yang Vincent W
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M402877200
Published
2004-06-18
Epub
2004-00-14
Pages
26707-15
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC1351009
Subset
IM
Grants
NIDDK NIH HHS · R01 DK052230 · United States
NIDDK NIH HHS · R01 DK055850 · United States
NIDDK NIH HHS · DK64399 · United States
NCI NIH HHS · R01 CA084197 · United States
NIDDK NIH HHS · R24 DK064399 · United States
NIDDK NIH HHS · DK52230 · United States
NIDDK NIH HHS · DK55850 · United States
NCI NIH HHS · CA84197 · United States
External Links
PubMed source DOI: 10.1074/jbc.M402877200 PMC Full Text View journal details
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