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Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis

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 beta-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 cel...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2007-08, Vol.67 (16), p.7703-7712
Main Authors: GAVERT, Nancy, SHEFFER, Michal, BEN-ZE'EV, Avri, RAVEN, Shani, SPADERNA, Simone, SHTUTMAN, Michael, BRABLETZ, Thomas, BARANY, Francis, PATY, Phillip, NOTTERMAN, Daniel, DOMANY, Eytan
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Language:English
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Summary: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 beta-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 beta-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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-07-0991