CSN5 Promotes Renal Cell Carcinoma Metastasis and EMT by Inhibiting ZEB1 Degradation

Biochem Biophys Res Commun. 2017 Jun 17;488(1):101-108. doi: 10.1016/j.bbrc.2017.05.016. Epub 2017 May 4.

Abstract

CSN5 (also known as COPS5) is a newly characterized oncogene involved in various types of cancer. However, its expression pattern and biological functions in renal cell carcinoma (RCC) is unknown. Here, we found that CSN5 expression was elevated in RCC tissues than those in paired normal renal tissues. Additionally, we demonstrated that high CSN5 level was closely correlated with tumor progression and poor survival in RCC patients. Our results showed that increased expression of CSN5 was observed in RCC cell lines and knockdown of CSN5 significantly suppressed the migration and invasion of RCC cells in vitro and in vivo. Additionally, CSN5 contributes to the metastasis and EMT (epithelial-mesenchymal transition) of RCC cells. Further investigation revealed that CSN5 led to the metastasis and EMT activation of RCC cells through increasing ZEB1 expression. Mechanistically, we found that CSN5 directly bound ZEB1 and decreased its ubiquitination to enhance the protein stability of ZEB1 in RCC cells. Taken together, our data identified CSN5 as a critical oncoprotein involved in migration and invasion of RCC cells, which could serve as a potential therapeutic target in RCC patients.

Keywords: CSN5; EMT; Invasion; Renal cell carcinoma; ZEB1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COP9 Signalosome Complex
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism*
  • Protein Stability
  • Tumor Cells, Cultured
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex