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REGγ deficiency suppresses tumor progression via stabilizing CK1ε in renal cell carcinoma

Shaojun Chen1,2, Qingwei Wang2, Longsheng Wang1

  • 1Department of Urology, Shanghai Tenth People's Hospital, Tongji University, 200072, Shanghai, China.

Cell Death & Disease
|May 26, 2018
PubMed

Insights

The proteasome activator REGγ is upregulated in kidney cancer (RCC), promoting tumor growth. Inhibiting REGγ suppressed RCC progression by stabilizing CK1ε and activating the Hippo pathway, suggesting new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Renal cell carcinoma (RCC) is a prevalent adult kidney malignancy.
  • The proteasome activator REGγ is implicated in various human cancers.
  • REGγ's role in RCC progression requires further elucidation.

Purpose of the Study:

  • To investigate the role of REGγ in renal cell carcinoma (RCC) development.
  • To identify novel targets and pathways regulated by REGγ in RCC.
  • To explore REGγ as a potential therapeutic target for RCC.

Main Methods:

  • Assessed REGγ expression levels in RCC tissues and correlated with patient prognosis.
  • Utilized in vitro and in vivo models to study the effect of REGγ depletion on RCC cells.
  • Identified and validated casein kinase 1ε (CK1ε) as a direct target of REGγ.
  • Investigated the impact of REGγ/CK1ε axis on the Hippo signaling pathway.

Main Results:

  • REGγ was found to be upregulated in RCC, correlating with poor patient prognosis.
  • REGγ depletion significantly inhibited RCC cell proliferation both in vitro and in vivo.
  • Casein kinase 1ε (CK1ε) was identified as a novel target of REGγ; its knockdown counteracted REGγ depletion effects.
  • REGγ depletion activated the Hippo signaling pathway by stabilizing CK1ε in RCC.

Conclusions:

  • REGγ plays a critical role in renal cell carcinoma (RCC) pathogenesis.
  • The REGγ/CK1ε axis interacts with the Hippo pathway in RCC development.
  • Targeting REGγ may offer a promising therapeutic strategy for RCC treatment.

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