title: DLC-1, a GTPase-activating protein for Rho, is associated with cell proliferation, morphology, and migration in human hepatocellular carcinoma.
abstract: DLC-1 (deleted in liver cancer-1) is a tumor suppressor gene for hepatocellular carcinoma and other cancers. To characterize its functions, we constructed recombinant adenovirus encoding the wild-type DLC-1 and examined its effects on behaviors of a hepatocellular carcinoma cell line (SNU-368), which does not express DLC-1. Here, we found that restoration of DLC-1 expression in the SNU-368 cells caused an inhibition of cell proliferation with an increase of a subG1 population. Furthermore, DLC-1 overexpression induced disassembly of stress fibers and extensive membrane protrusions around cells on laminin-1. DLC-1 overexpression also inhibited cell migration and dephosphorylated focal adhesion proteins such as focal adhesion kinase (FAK), Cas (p130Cas; Crk-associated substrate), and paxillin. These observations suggest that DLC-1 plays important roles in signal transduction pathway regulating cell proliferation, cell morphology, and cell migration by affecting Rho family GTPases and focal adhesion proteins.
authors.affiliation: National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea.
authors.forename: Tai Young
authors.initials: TY
authors.lastname: Kim
authors.forename: Jung Weon
authors.initials: JW
authors.lastname: Lee
authors.forename: Hwang-Phill
authors.initials: HP
authors.lastname: Kim
authors.forename: Hyun-Soon
authors.initials: HS
authors.lastname: Jong
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.forename: Mira
authors.initials: M
authors.lastname: Jung
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D020690:GTPase-Activating Proteins; D006801:Humans; D007668:Kidney; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins