title: Experimental evidence of Migfilin as a new therapeutic target of hepatocellular carcinoma metastasis.
abstract: Migfilin is a novel cell-matrix adhesion protein known to interact with Vasodilator Stimulated Phosphoprotein (VASP) and be localized both at cell-matrix and cell-cell adhesions. To date there is nothing known about its role in hepatocellular carcinoma (HCC). As matrix is important in metastasis, we aimed to investigate the Migfilin׳s role in HCC metastasis using two human HCC cell lines that differ in their metastatic potential; non-invasive Alexander cells and the highly invasive HepG2 cells. We silenced Migfilin by siRNA and studied its effect on signaling and metastasis-related cellular properties. We show that Migfilin׳s expression is elevated in HepG2 cells and its silencing leads to upregulation of actin reorganization-related proteins, namely phosphor-VASP (Ser157 and Ser239), Fascin-1 and Rho-kinase-1, promoting actin polymerization and inhibiting cell invasion. Phosphor-Akt (Ser473) is decreased contributing to the upregulation of free and phosphor-β-catenin (Ser33/37Thr41) and inducing proliferation. Migfilin elimination upregulates Extracellular Signal-regulated kinase, which increases cell adhesion in HepG2 and reduces invasiveness. This is the first study to reveal that Migfilin inhibition can halt HCC metastasis in vitro, providing the molecular mechanism involved and presenting Migfilin as potential therapeutic target against HCC metastasis.
authors.affiliation: Department of Biomedical Research and Technology, Institute for Research and Technology-Thessaly, Centre for Research and Technology-Hellas (CE.R.T.H.), Larissa 41222, Greece. Electronic address: vasso.gkretsi@gmail.com.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Gkretsi
authors.affiliation: Department of Biomedical Research and Technology, Institute for Research and Technology-Thessaly, Centre for Research and Technology-Hellas (CE.R.T.H.), Larissa 41222, Greece; Department of Rheumatology, School of Medicine, University of Thessaly, University Hospital of Larissa, 41110 Larissa, Greece; Institute of Liver Studies, King׳s College Hospital, Denmark Hill, London SE5 9RS, UK.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Bogdanos
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C473794:FBLIM1 protein, human
keywords: Adhesion; Fascin-1; Hepatocellular carcinoma; Invasion; Metastasis; Migfilin; VASP