Effect of ubiquitin protease system on DNA damage response in prostate cancer (Review)

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Genomic instability is a hallmark of cancer, often driven by defects in cellular DNA damage response (DDR).
• Dysfunctional ubiquitin-proteasome system (UPS) is a common event in metastatic castration-resistant prostate cancer (PCa), impacting DDR.
• Specific UPS components like Speckle-type BTB/POZ protein, Skp2, and ubiquitin-specific protease 12 are implicated in DDR alterations.

Purpose of the Study:

• To review the fundamental pathways of DDR and UPS dysfunction.
• To elucidate how UPS dysfunction induces DDR alterations and genomic instability.
• To explore the potential of UPS and DDR alterations as biomarkers and therapeutic targets in PCa.

Main Methods:

• Literature review of studies on DDR, UPS, and their roles in cancer.
• Analysis of molecular mechanisms linking UPS dysfunction to DDR defects.
• Examination of existing and potential applications in prostate cancer treatment.

Main Results:

• Mutations in Speckle-type BTB/POZ protein impair DDR.
• Skp2 upregulation inhibits DNA repair and promotes cancer cell growth and migration.
• USP12 overexpression leads to p53 degradation, interrupting DDR and causing genomic instability.

Conclusions:

• UPS dysfunction is a critical driver of genomic instability and DDR defects in cancer, especially PCa.
• Understanding these molecular events is crucial for developing novel therapeutic strategies.
• UPS and DDR alterations hold significant promise as biomarkers and therapeutic targets for prostate cancer.