Selenoprotein W Inhibits the c-Met Oncogene by Regulating Receptor Ubiquitination

Background: Hepatocyte Growth Factor Receptor (HGFR), or c-Met, is the receptor for Hepatocyte Growth Factor (HGF). HGF-bound c-Met causes the activation of many important downstream pathways leading to cell proliferation, survival, invasion, differentiation, and migration. Selenoprotein W1 (SEPW1) is a selenium (Se) regulated, small thioredoxin-like protein required for cell cycle entry in breast and prostate epithelial cells. Se is an essential micronutrient with an involvement in cancer, but the mechanisms of its action are unclear. Low levels of dietary Se can be a risk factor for many cancers including liver cancer. The objective of this study was to investigate the mechanisms by which SEPW1 inhibits the invasive properties of hepatocellular carcinoma in HepG2 cells. Results: Silencing SEPW1 caused an increase in total c-Met expression, c-Met located on the plasma membrane, and HGF-induced c-Met phosphorylation in HepG2 human hepatocellular carcinoma cells. Consistent with the increase in total c-Met...