Abstract
We conducted a study concerning the suppressive mechanism of KAI1/CD82 on hepatoma cell metastasis. Hepatocyte growth factor (HGF) induces the migration of hepatoma cells through activation of cellular sphingosine kinase 1 (SphK1). Adenovirus-mediated gene transfer of KAI1 (Ad-KAI1) downregulates the SphK1 expression and suppresses the HGF-induced migration of SMMC-7721 human hepatocellcular carcinoma cells. Overexpression of KAI1/CD82 significantly elevates Sprouty2 at the protein level. Ablation of Sprouty2 with RNA interference can block the KAI1/CD82-induced suppression of hepatoma cell migration and downregulation of SphK1 expression. It is demonstrated that KAI1/CD82 suppresses HGF-induced migration of hepatoma cells via upregulation of Sprouty2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism*
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Carcinoma, Hepatocellular / pathology*
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Cell Line, Tumor
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Cell Movement / drug effects*
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Enzyme Activation
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Hepatocyte Growth Factor / pharmacology*
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Kangai-1 Protein / genetics
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Kangai-1 Protein / metabolism*
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Membrane Proteins
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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RNA, Small Interfering / genetics
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Up-Regulation / drug effects*
Substances
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Intracellular Signaling Peptides and Proteins
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Kangai-1 Protein
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Membrane Proteins
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RNA, Small Interfering
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SPRY2 protein, human
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Hepatocyte Growth Factor
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Phosphotransferases (Alcohol Group Acceptor)
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sphingosine kinase