Conclusion
Based on these findings, we conclude that CHIP is a suppressor of Met function, serving to regulate cellular receptor levels by promoting Met receptor degradation.
Methods
Here, we describe a novel mechanism of Met degradation in Non Small Cell Lung Cancer Cells and HeLa cells using western blot, immunocytochemistry, immunoprecipitation assay, invasion assay, cell viability assay and in vivo tumor growth model.
Results
Met receptor interacted with the C-terminus of heat shock protein 70-interacting protein (CHIP), leading to proteasomal degradation of the receptor in vitro. In addition, CHIP overexpression destabilized endogenous Met receptor in lung cancer cells, whereas CHIP knockdown increased Met receptor expression, indicating an essential role for CHIP in the regulation of Met degradation. CHIP overexpression inhibited Met-mediated lung cancer cell growth and invasion. Finally, we confirmed these results by tumor xenograft model.