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OTUB1 promotes esophageal squamous cell carcinoma metastasis through modulating Snail stability

Honghong Zhou1,2, Yongshuo Liu1, Rui Zhu1

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

Oncogene
|March 22, 2018
PubMed

Insights

Ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1) stabilizes Snail, a key protein in cancer metastasis. High OTUB1 levels promote esophageal squamous cell carcinoma (ESCC) progression and indicate a poor prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Snail protein regulates epithelial-mesenchymal transition (EMT), crucial for tumor progression and metastasis.
  • Snail protein undergoes rapid degradation, with its levels tightly controlled.
  • While E3 ligases targeting Snail are known, the deubiquitinases (DUBs) involved in Snail deubiquitination remain understudied.

Purpose of the Study:

  • To identify deubiquitinases (DUBs) that regulate Snail protein stability.
  • To investigate the role of ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1) in Snail deubiquitination and cancer progression.

Main Methods:

  • Protein stability assays to assess Snail degradation.
  • Ubiquitination assays to detect Snail modification.
  • Immunohistochemistry to evaluate OTUB1 expression in esophageal squamous cell carcinoma (ESCC) tissues.
  • Bioinformatic analysis to correlate OTUB1 expression with patient prognosis.

Main Results:

  • Ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1) was identified as a deubiquitinase that stabilizes Snail.
  • OTUB1 prevents Snail ubiquitination and subsequent proteasomal degradation, thereby increasing Snail protein levels.
  • OTUB1 overexpression was observed in ESCC tissues and correlated with advanced tumor stage and poor patient survival.
  • OTUB1 promotes Snail-dependent metastasis in esophageal squamous cell carcinoma (ESCC).

Conclusions:

  • OTUB1 stabilizes Snail protein by inhibiting its ubiquitination and proteasomal degradation.
  • OTUB1 plays a critical role in facilitating esophageal squamous cell carcinoma (ESCC) metastasis through Snail stabilization.
  • High OTUB1 expression serves as a potential prognostic biomarker for esophageal cancer.

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