Related Experiment Video

Updated: Feb 20, 2026

TGF-β-mediated Endothelial to Mesenchymal Transition EndMT and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing
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TGF-β-mediated Endothelial to Mesenchymal Transition EndMT and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing

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SPSB3 targets SNAIL for degradation in GSK-3β phosphorylation-dependent manner and regulates metastasis

Y Liu1, H Zhou1, R Zhu1

  • 1State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.

Oncogene
|October 24, 2017
PubMed

Insights

Scientists discovered that SPSB3 protein degrades SNAIL, a key factor in cancer spread. This finding offers new insights into controlling epithelial-mesenchymal transition (EMT) and cancer progression, potentially improving patient survival.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Epithelial-mesenchymal transition (EMT) is crucial for cancer initiation and progression.
  • SNAIL, a zinc finger transcription factor, is a key regulator of EMT.
  • Understanding SNAIL's regulation is vital for developing cancer therapies.

Purpose of the Study:

  • To identify novel regulators of SNAIL.
  • To investigate the role of E3 ligases in SNAIL degradation.
  • To explore the therapeutic potential of targeting SNAIL regulation in cancer.

Main Methods:

  • Genome-wide screening using a small interfering RNA library against E3 ligases and ubiquitin-related genes.
  • Luciferase-based assay to identify SNAIL regulators.
  • In vitro and in vivo experiments to assess the function of identified regulators.
  • Analysis of patient tissues to correlate gene expression with clinical outcomes.

Main Results:

  • SOCS box protein SPSB3 was identified as a novel E3 ligase targeting SNAIL for degradation.
  • SPSB3 promotes SNAIL polyubiquitination and degradation, particularly after GSK-3β phosphorylation of SNAIL.
  • SPSB3 overexpression inhibits tumor metastasis in vitro and in vivo.
  • SPSB3 and SNAIL expression are negatively correlated in esophageal squamous cell carcinoma.
  • Low SPSB3 expression correlates with lymph node metastasis and poor survival in various cancers.

Conclusions:

  • SPSB3-mediated SNAIL degradation is a critical mechanism regulating EMT and cancer progression.
  • SPSB3 acts as a tumor suppressor by inhibiting metastasis.
  • SPSB3 expression levels can serve as a prognostic biomarker for various cancers.
  • Targeting the SPSB3-SNAIL axis presents a potential therapeutic strategy for cancer treatment.

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