PuSH - Publication Server of Helmholtz Zentrum München

Kühn, S.* ; Koch, M.* ; Nübel, T.* ; Ladwein, M.* ; Antolovic, D.* ; Klingbeil, P.* ; Hildebrand, D.* ; Moldenhauer, G.* ; Langbein, L.* ; Franke, W.W.* ; Weitz, J.* ; Zöller, M.*

A complex of EpCAM, claudin-7, CD44 variant isoforms, and tetraspanins promotes colorectal cancer progression.

Mol. Cancer Res. 5, 553-567 (2007)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
High expression of EpCAM and the tetraspanin CO-029 has been associated with colorectal cancer progression. However, opposing results have been reported on CD44 variant isoform v6 (CD44v6) expression. We recently noted in rat gastrointestinal tumors that EpCAM, claudin-7, CO-029, and CD44v6 were frequently coexpressed and could form a complex. This finding suggested the possibly that the complex, rather than the individual molecules, could support tumor progression. The expression of EpCAM, claudin-7, CO-029, and CD44v6 expression was evaluated in colorectal cancer (n = 104), liver metastasis (n = 66), and tumor-free colon and liver tissue. Coexpression and complex formation of the molecules was correlated with clinical variables and apoptosis resistance. EpCAM, claudin-7, CO-029, and CD44v6 expression was up-regulated in colon cancer and liver metastasis. Expression of the four molecules did not correlate with tumor staging and grading. However, coexpression inversely correlated with disease-free survival. Coexpression was accompanied by complex formation and recruitment into tetraspanin-enriched membrane microdomains (TEM). Claudin-7 contributes to complex formation inasmuch as in the absence of claudin-7, EpCAM hardly associates with CO-029 and CD44v6 and is not recruited into TEMs. Notably, colorectal cancer lines that expressed the EpCAM/claudin-7/CO-029/CD44v6 complex displayed a higher degree of apoptosis resistance than lines devoid of any one of the four molecules. Expression of EpCAM, claudin-7, CO-029, and CD44v6 by themselves cannot be considered as prognostic markers in colorectal cancer. However, claudin-7-associated EpCAM is recruited into TEM and forms a complex with CO-029 and CD44v6 that facilitates metastasis formation.
Impact Factor
Scopus SNIP
Altmetric
0.000
0.000
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2007
HGF-reported in Year 0
ISSN (print) / ISBN 1541-7786
e-ISSN 1557-3125
Quellenangaben Volume: 5, Issue: 6, Pages: 553-567 Article Number: , Supplement: ,
Publisher American Association for Cancer Research (AACR)
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
PubMed ID 17579117
Erfassungsdatum 2007-12-31