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KAI1/CD82 suppresses hepatocyte growth factor-induced migration of hepatoma cells via upregulation of Sprouty2
Authors:ZhenBin Mu  Hua Wang  Jing Zhang  QingFang Li  LiSheng Wang  XiaoZhong Guo
Affiliation:(1) Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;(2) Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;(3) Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA;(4) Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;(5) National Foundation for Cancer Research—Center for Metastasis Research, University of Alabama at Birmingham, Birmingham, AL 35294, USA;(6) University of Alabama at Birmingham, G-019 Volker Hall, 1670 University Blvd., Birmingham, AL 35294, USA;
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.
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