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Cell, Tumor, and Stem Cell Biology |
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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S. E. James, P. D. Greenberg, M. C. Jensen, Y. Lin, J. Wang, B. G. Till, A. A. Raubitschek, S. J. Forman, and O. W. Press Antigen Sensitivity of CD22-Specific Chimeric TCR Is Modulated by Target Epitope Distance from the Cell Membrane J. Immunol., May 15, 2008; 180(10): 7028 - 7038. [Abstract] [Full Text] [PDF] |
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Correction: L1-CAM and ADAM10 Induce Metastasis in Colon Cancer Cancer Res., November 1, 2007; 67(21): 10624 - 10625. [Full Text] [PDF] |
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