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Cancer Research 67, 7703-7712, August 15, 2007. doi: 10.1158/0008-5472.CAN-07-0991
© 2007 American Association for Cancer Research

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Cell, Tumor, and Stem Cell Biology

Expression of L1-CAM and ADAM10 in Human Colon Cancer Cells Induces Metastasis

Nancy Gavert1, Michal Sheffer2, Shani Raveh1, Simone Spaderna3, Michael Shtutman4, Thomas Brabletz3, Francis Barany5, Phillip Paty6, Daniel Notterman7, Eytan Domany2 and Avri Ben-Ze'ev1

Departments of 1 Molecular Cell Biology and 2 Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel; 3 Department of Pathology, University of Erlangen-Nürnberg, Erlangen, Germany; 4 Cancer Center, Ordway Research Institute, Albany, New York; 5 Department of Microbiology, Weill Medical College, Cornell University; 6 Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York; and 7 Departments of Pediatrics and Molecular Genetics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey

Requests for reprints: Avri Ben-Ze'ev, Department of Molecular Cell Biology, Weizmann Institute of Science, P. O. Box 26, Rehovot, Israel. Phone: 972-8-9342422; Fax: 972-8-9465261; E-mail: avri.ben-zeev{at}weizmann.ac.il.

L1-CAM, a neuronal cell adhesion receptor, is also expressed in a variety of cancer cells. Recent studies identified L1-CAM as a target gene of ß-catenin-T-cell factor (TCF) signaling expressed at the invasive front of human colon cancer tissue. We found that L1-CAM expression in colon cancer cells lacking L1-CAM confers metastatic capacity, and mice injected in their spleen with such cells form liver metastases. We identified ADAM10, a metalloproteinase that cleaves the L1-CAM extracellular domain, as a novel target gene of ß-catenin-TCF signaling. ADAM10 overexpression in colon cancer cells displaying endogenous L1-CAM enhanced L1-CAM cleavage and induced liver metastasis, and ADAM10 also enhanced metastasis in colon cancer cells stably transfected with L1-CAM. DNA microarray analysis of genes induced by L1-CAM in colon cancer cells identified a cluster of genes also elevated in a large set of human colon carcinoma tissue samples. Expression of these genes in normal colon epithelium was low. These results indicate that there is a gene program induced by L1-CAM in colon cancer cells that is also present in colorectal cancer tissue and suggest that L1-CAM can serve as target for colon cancer therapy. [Cancer Res 2007;67(16):7703–12]




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Correction: L1-CAM and ADAM10 Induce Metastasis in Colon Cancer
Cancer Res., November 1, 2007; 67(21): 10624 - 10625.
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2007 by the American Association for Cancer Research.