The ubiquitin ligase CHIP inactivates NF-κB signaling and impairs the ability of migration and invasion in gastric cancer cells

Liu,Fei; Zhou,Jun; Zhou,Peng; Chen,Weichang; Guo,Feng

doi:10.3892/ijo.2015.2893

The ubiquitin ligase CHIP inactivates NF-κB signaling and impairs the ability of migration and invasion in gastric cancer cells

Authors:
- Fei Liu
- Jun Zhou
- Peng Zhou
- Weichang Chen
- Feng Guo
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Affiliations: Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, P.R. China
Published online on: February 11, 2015 https://doi.org/10.3892/ijo.2015.2893
Pages: 2096-2106

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Abstract

Ubiquitin modification of proteins influences cellular processes related to carcinogenesis. The carboxyl terminus of Hsc-70-interacting protein (CHIP), as U-box-type ubiquitin ligase, induces ubiquitination and proteasome-mediated degradation of its substrate proteins. In this study, the role of CHIP in diverse aspects of gastric cancer cells was investigated. CHIP overexpression in the AGS gastric cancer cells caused impaired tumor growth. CHIP overexpression significantly inhibited the migration and invasion of the AGS cells. Moreover, we found that not only RelA/p65 but also RelB, the NF-κB subunits, was negatively regulated by CHIP, likely owing to the TRAF2 reduction. Downregulated target genes of NF-κB subunits, including MMP-2 and -9, integrin β-1 and Bcl-2 were involved in these processes. We also showed that the expression level of CHIP was frequently decreased in gastric cancer tissues and the low level of CHIP expression might be an indicator of an unfavorable prognosis. Taken together, these observations provide functional evidence for CHIP behaviors as a tumor suppressor in gastric cancer.

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