Abstract
Multiple SRC-family kinases (SFKs) are commonly activated in carcinoma and appear to have a role in metastasis through incompletely understood mechanisms. Recent studies have shown that CDCP1 (CUB (complement C1r/C1s, Uegf, Bmp1) Domain-Containing Protein-1) is a transmembrane protein and an SRC substrate potentially involved in metastasis. Here we show that increased SFK and CDCP1 tyrosine phosphorylation is, surprisingly, associated with a decrease in FAK phosphorylation. This appears to be true in human tumors as shown by our correlation analysis of a mass spectrometric data set of affinity-purified phosphotyrosine peptides obtained from normal and cancer lung tissue samples. Induction of tyrosine phosphorylation of CDCP1 in cell culture, including by a mAb that binds to its extracellular domain, promoted changes in SFK and FAK tyrosine phosphorylation, as well as in PKC(TM), a protein known to associate with CDCP1, and these changes are accompanied by increases in adhesion and motility. Thus, signaling events that accompany the CDCP1 tyrosine phosphorylation observed in cell lines and human lung tumors may explain how the CDCP1/SFK complex regulates motility and adhesion.
MeSH terms
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Antigens, CD / genetics
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Antigens, CD / immunology
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Antigens, CD / metabolism*
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Antigens, Neoplasm
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Cell Adhesion / drug effects
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Cell Adhesion / genetics
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Cell Adhesion / physiology
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / immunology
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Cell Adhesion Molecules / metabolism*
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Cell Communication / drug effects
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Cell Communication / genetics
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Cell Communication / physiology
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Cell Line
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Movement / genetics
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Cell Movement / physiology*
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Enzyme Activation / drug effects
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Focal Adhesion Kinase 1 / metabolism
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HCT116 Cells
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Humans
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Immunoblotting
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Immunoprecipitation
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mutation
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Neoplasm Proteins / genetics
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Neoplasm Proteins / immunology
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Neoplasm Proteins / metabolism*
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Phosphorylation / drug effects
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Protein Binding
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Protein Kinase C / metabolism
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RNA Interference
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Signal Transduction / physiology
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Tyrosine / genetics
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Tyrosine / metabolism
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src-Family Kinases / metabolism*
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Neoplasm
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CDCP1 protein, human
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Cell Adhesion Molecules
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Neoplasm Proteins
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Tyrosine
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Focal Adhesion Kinase 1
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PTK2 protein, human
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src-Family Kinases
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Protein Kinase C