Reciprocal Activating Crosstalk between c-Met and Caveolin 1 Promotes Invasive Phenotype in Hepatocellular Carcinoma |
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| Authors: | Peyda Korhan Esra Erdal Emine Kandemi? Murat ?okakl? Deniz Nart Funda Y?lmaz Alp Can Ne?e Atabey |
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| Affiliation: | 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.; Xiangya Hospital of Central South University, China, |
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| 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. |
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