Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis Journal Article
| Authors: | Gavert, N.; Sheffer, M.; Raveh, S.; Spaderna, S.; Shtutman, M.; Brabletz, T.; Barany, F.; Paty, P.; Notterman, D.; Domany, E.; Ben-Ze'ev, A. |
| Article Title: | Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis |
| Abstract: | 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 β-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 β-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. ©2007 American Association for Cancer Research. |
| Keywords: | immunohistochemistry; signal transduction; controlled study; protein expression; unclassified drug; human cell; cancer growth; nonhuman; liver neoplasms; mouse; metastasis; reverse transcription polymerase chain reaction; protein degradation; animal experiment; animal model; colonic neoplasms; hct116 cells; membrane proteins; immunofluorescence; in vitro study; cell line, tumor; transfection; gene expression regulation; liver metastasis; amino acid sequence; cell culture; colon cancer; gene identification; cancer cell; cell growth processes; western blotting; dna microarray; beta catenin; metalloproteinase; adam protein; adam proteins; amyloid precursor protein secretases; nerve cell adhesion molecule l1; neural cell adhesion molecule l1; protein adam 10 |
| Journal Title: | Cancer Research |
| Volume: | 67 |
| Issue: | 16 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2007-08-15 |
| Start Page: | 7703 |
| End Page: | 7712 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-07-0991 |
| PUBMED: | 17699774 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 54" - "Export Date: 17 November 2011" - "CODEN: CNREA" - "Source: Scopus" |
