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SIRT5 Directly Inhibits the PI3K/AKT Pathway in Prostate Cancer Cell Lines

So Young Choi1, Ju Mi Jeon1, Ann Yae Na1

  • 1BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea.

Cancer Genomics & Proteomics
|December 24, 2021
PubMed
Abstract

Insights

This study reveals that decreased SIRT5 levels correlate with prostate cancer (PCa) metastasis. Loss of SIRT5 activates the PI3K/AKT/NF-κB pathway, promoting cancer spread.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Prostate cancer (PCa) is a leading cancer in men, with bone metastasis significantly reducing survival.
  • Mechanisms of PCa metastasis are not fully understood.
  • SIRT5, an NAD+-dependent deacylase, plays a role in various cancers, but its function in PCa is understudied.

Purpose of the Study:

  • To investigate the role of SIRT5 in prostate cancer metastasis.
  • To identify molecular mechanisms linking SIRT5 to PCa progression.

Main Methods:

  • Quantitative proteomics to compare protein expression between parental and SIRT5 knockout PC-3 cells.
  • Bioinformatic analysis (Gene Ontology, KEGG pathway) for functional enrichment.
  • Immunoprecipitation to confirm protein interactions.

Main Results:

  • SIRT5 levels were significantly decreased in aggressive PC-3M cells.
  • SIRT5 knockout cells showed increased interleukin-1β (IL-1β) expression.
  • The PI3K/AKT/NF-κB signaling pathway was upregulated in SIRT5 knockout cells.
  • SIRT5 was found to bind to PI3K.

Conclusions:

  • This is the first study to link SIRT5 to prostate cancer metastasis.
  • Reduced SIRT5 function may promote PCa metastasis by inhibiting the PI3K/AKT/NF-κB pathway.
  • This pathway dysregulation could drive secondary metastasis from bone to other tissues.
Keywords:
IL-1BPI3K/AKT pathwayProstate cancerSIRT5metastasis

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