title: The ubiquitin ligase CHIP inactivates NF-κB signaling and impairs the ability of migration and invasion in gastric cancer cells.
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.
authors: Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, P.R. China.
authors: Fei
authors: F
authors: Liu
authors: Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, P.R. China.
authors: Jun
authors: J
authors: Zhou
authors: Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, P.R. China.
authors: Peng
authors: P
authors: Zhou
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, P.R. China.
authors: Weichang
authors: W
authors: Chen
authors: Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, P.R. China.
authors: Feng
authors: F
authors: Guo
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000473:pathology*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; C467728:STUB1 protein, human; D044767:Ubiquitin-Protein Ligases