Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma

Peyda Korhan; Esra Erdal; Emine Kandemiş; Murat Cokaklı; Deniz Nart; Funda Yılmaz; Alp Can; Neşe Atabey

doi:10.1371/journal.pone.0105278

Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma

PLoS One. 2014 Aug 22;9(8):e105278. doi: 10.1371/journal.pone.0105278. eCollection 2014.

Authors

Peyda Korhan¹, Esra Erdal¹, Emine Kandemiş¹, Murat Cokaklı¹, Deniz Nart², Funda Yılmaz², Alp Can³, Neşe Atabey¹

Affiliations

¹ Department of Medical Biology, Dokuz Eylul University Medical School, Izmir, Turkey.
² Department of Pathology, School of Medicine, Ege University, Izmir, Turkey.
³ Department of Histology and Embryology, School of Medicine, Ankara University, Ankara, Turkey.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism*
Carcinoma, Hepatocellular / pathology*
Caveolin 1 / metabolism*
Cell Line, Tumor
Cell Movement / drug effects
Cell Movement / genetics
Gene Expression Regulation, Neoplastic / drug effects
Gene Silencing
Hepatocyte Growth Factor / pharmacology
Humans
Liver Cirrhosis / genetics
Liver Cirrhosis / metabolism
Liver Cirrhosis / pathology
Liver Neoplasms / genetics
Liver Neoplasms / metabolism*
Liver Neoplasms / pathology*
Neoplasm Invasiveness
Phosphorylation
Protein Binding
Protein Transport
Proto-Oncogene Proteins c-met / agonists
Proto-Oncogene Proteins c-met / antagonists & inhibitors
Proto-Oncogene Proteins c-met / metabolism*
RNA Interference
Signal Transduction

Substances

Caveolin 1
Hepatocyte Growth Factor
Proto-Oncogene Proteins c-met

Grants and funding

This project was funded by grants to Prof. Dr. Atabey from Turkish Scientific and Technological Research Council (TUBITAK, SBAG-107S026) and Dokuz Eylul University Research Foundation (05.KB.SAG.71). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.