title: Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.
abstract: c-Met, the receptor for Hepatocyte Growth Factor (HGF), overexpressed and deregulated in Hepatocellular Carcinoma (HCC). Caveolin 1 (CAV1), a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.
authors.affiliation: Department of Medical Biology, Dokuz Eylul University Medical School, Izmir, Turkey.
authors.forename: Peyda
authors.initials: P
authors.lastname: Korhan
authors.affiliation: Department of Medical Biology, Dokuz Eylul University Medical School, Izmir, Turkey.
authors.forename: Esra
authors.initials: E
authors.lastname: Erdal
authors.affiliation: Department of Medical Biology, Dokuz Eylul University Medical School, Izmir, Turkey.
authors.forename: Emine
authors.initials: E
authors.lastname: Kandemiş
authors.affiliation: Department of Medical Biology, Dokuz Eylul University Medical School, Izmir, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Cokaklı
authors.affiliation: Department of Pathology, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Nart
authors.affiliation: Department of Pathology, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Funda
authors.initials: F
authors.lastname: Yılmaz
authors.affiliation: Department of Histology and Embryology, School of Medicine, Ankara University, Ankara, Turkey.
authors.forename: Alp
authors.initials: A
authors.lastname: Can
authors.affiliation: Department of Medical Biology, Dokuz Eylul University Medical School, Izmir, Turkey.
authors.forename: Neşe
authors.initials: N
authors.lastname: Atabey
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051242:Caveolin 1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D019859:Proto-Oncogene Proteins c-met / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D051242:Caveolin 1; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met