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

Nancy Gavert, Michal Sheffer, Shani Raveh, Simone Spaderna, Michael Shtutman, Thomas Brabletz, Francis Barany, Phillip Paty, Daniel Notterman, Eytan Domany, Avri Ben-Ze'ev

Research output: Contribution to journalArticle

139 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7703-7712
Number of pages10
JournalCancer Research
Volume67
Issue number16
DOIs
StatePublished - Aug 15 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Gavert, N., Sheffer, M., Raveh, S., Spaderna, S., Shtutman, M., Brabletz, T., Barany, F., Paty, P., Notterman, D., Domany, E., & Ben-Ze'ev, A. (2007). Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis. Cancer Research, 67(16), 7703-7712. https://doi.org/10.1158/0008-5472.CAN-07-0991