Abstract
Aberrant beta-catenin-TCF target gene activation plays a key role in colorectal cancer, both in the initiation stage and during invasion and metastasis. We identified the neuronal cell adhesion molecule L1, as a target gene of beta-catenin-TCF signaling in colorectal cancer cells. L1 expression was high in sparse cultures and coregulated with ADAM10, a metalloprotease involved in cleaving and shedding L1's extracellular domain. L1 expression conferred increased cell motility, growth in low serum, transformation and tumorigenesis, whereas its suppression in colon cancer cells decreased motility. L1 was exclusively localized in the invasive front of human colorectal tumors together with ADAM10. The transmembrane localization and shedding of L1 by metalloproteases could be useful for detection and as target for colon cancer therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADAM Proteins
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ADAM10 Protein
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Amyloid Precursor Protein Secretases
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Animals
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Cell Movement / genetics
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Cell Movement / physiology*
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Cell Proliferation
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism*
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Colonic Neoplasms / genetics
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Colonic Neoplasms / metabolism*
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Cytoskeletal Proteins / metabolism*
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Humans
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Immunohistochemistry
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Membrane Proteins
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Metalloendopeptidases
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Mice
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NIH 3T3 Cells
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Neural Cell Adhesion Molecule L1 / genetics
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Neural Cell Adhesion Molecule L1 / metabolism*
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Promoter Regions, Genetic / genetics
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RNA, Small Interfering / metabolism
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Signal Transduction / genetics
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Signal Transduction / physiology
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Trans-Activators / metabolism*
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Tumor Cells, Cultured
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beta Catenin
Substances
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CTNNB1 protein, human
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CTNNB1 protein, mouse
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Cytoskeletal Proteins
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Membrane Proteins
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Neural Cell Adhesion Molecule L1
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RNA, Small Interfering
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Trans-Activators
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beta Catenin
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Amyloid Precursor Protein Secretases
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ADAM Proteins
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Metalloendopeptidases
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ADAM10 Protein
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ADAM10 protein, human