title: Phorbol ester-induced migration of HepG2 cells is accompanied by intensive stress fibre formation, enhanced integrin expression and transient down-regulation of p21-activated kinase 1.
abstract: Previously, we observed that phorbol ester induced more intensive scattering of HepG2 human hepatoma cells than hepatocyte growth factor (HGF). Regulatory components accounting for this intensive migration were studied. Phorbol ester-activated protein kinase C induced the early appearance of a great number of actin stress fibres. Whereas in response to HGF, the activation of phosphatidylinositol 3-kinase initiates the rearrangements of the actin cytoskeleton, in phorbol ester-treated cells, the activation of this enzyme was not required to the actin polymerisation. Activation of Erk1/Erk2 MAP kinases that was essential to the migration had a key role in enhancing the adherence of cells to the extracellular matrix via the increased expression of integrins alpha2, alpha6 and beta1. Protein kinase C stimulated the activation of p21-activated kinase (PAK), as well. However, it also stimulated the selective and transient down-regulation of PAK1, which coincided with the formation of stress fibres.
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University of Medicine, PO Box 260, 1444 Budapest, Hungary.
authors.forename: Annamária
authors.initials: A
authors.lastname: Gujdár
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Sipeki
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Bander
authors.forename: László
authors.initials: L
authors.lastname: Buday
authors.forename: Anna
authors.initials: A
authors.lastname: Faragó
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000201:enzymology; D002273:Carcinogens / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism; D039503:Integrin alpha6 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008113:Liver Neoplasms; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D022502:Stress Fibers / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D054462:p21-Activated Kinases
chemical_list: D002273:Carcinogens; D039421:Integrin alpha2; D039503:Integrin alpha6; D019012:Integrin beta1; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate