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E3 ligase Skp2-mediated stabilization of survivin contributes to radioresistance

Shiming Tan1,2, Ruirui Wang1, Jinglin Fang3

  • 1Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, China.

Cell Death Discovery
|April 8, 2025
PubMed

Insights

Targeting S-phase kinase-associated protein 2 (Skp2) can enhance radiotherapy sensitivity in oral squamous cell carcinoma (OSCC). Reducing Skp2 levels promotes apoptosis and overcomes treatment resistance in OSCC, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Oral squamous cell carcinoma (OSCC) is a common head and neck cancer.
  • Radiotherapy resistance is a significant clinical challenge in OSCC treatment.
  • S-phase kinase-associated protein 2 (Skp2) is implicated in various cancers.

Purpose of the Study:

  • To investigate the role of Skp2 in OSCC radiotherapy resistance.
  • To explore the potential of targeting Skp2 for radiosensitization in OSCC.
  • To elucidate the molecular mechanisms underlying Skp2's effect on OSCC radiosensitivity.

Main Methods:

  • Overexpression analysis of Skp2 in OSCC cells and tissues.
  • Skp2 knockdown experiments in OSCC cell lines.
  • Investigation of the Akt/Wee1/CDK1 axis and Survivin pathway.
  • Clinicopathologic analysis of Skp2, p-Akt, and Survivin expression in patient tissues.

Main Results:

  • Skp2 is overexpressed in OSCC and positively correlated with p-Akt and Survivin.
  • Skp2 knockdown significantly enhances OSCC cell radiosensitivity.
  • Skp2 inhibition induces apoptosis via the Akt/Wee1/CDK1 axis, affecting Survivin phosphorylation and degradation.
  • Targeting Skp2 overcomes radiotherapy resistance in OSCC models.

Conclusions:

  • Skp2 plays a crucial role in mediating radiotherapy resistance in OSCC.
  • Targeting the Skp2-Survivin axis is a promising strategy for enhancing OSCC radiosensitization.
  • Inhibition of Skp2 offers a potential therapeutic avenue for improving OSCC treatment outcomes.

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