Deubiquitinating enzyme PSMD14 promotes tumor metastasis through stabilizing SNAIL in human esophageal squamous cell...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• SNAIL, an EMT transcription factor, drives metastasis and poor prognosis in esophageal squamous cell carcinoma (ESCC).
• SNAIL protein levels are regulated by the ubiquitin-proteasome system, involving ubiquitination and degradation.
• The role of deubiquitination in regulating SNAIL stability and function remains largely uncharacterized.

Purpose of the Study:

• To identify deubiquitinating enzymes that interact with and regulate SNAIL.
• To investigate the functional role of identified deubiquitinating enzymes in esophageal cancer progression.
• To evaluate the potential of targeting these enzymes as a therapeutic strategy for esophageal cancer.

Main Methods:

• Mass spectrometry was employed to identify proteins interacting with SNAIL.
• Co-immunoprecipitation and Western blotting were used to confirm the interaction between SNAIL and PSMD14.
• Cell-based assays (in vitro) and animal models (in vivo) were utilized to assess the impact of PSMD14 modulation on tumor cell migration, invasion, and metastasis.
• Correlation analysis between PSMD14 expression and patient prognosis was performed.

Main Results:

• PSMD14 was identified as a deubiquitinating enzyme that directly targets SNAIL.
• PSMD14 deubiquitinates and stabilizes SNAIL, promoting epithelial-mesenchymal transition (EMT).
• Knockdown of PSMD14 inhibited SNAIL-induced EMT, suppressed tumor cell migration and invasion in vitro, and reduced metastasis in vivo.
• High PSMD14 expression correlated with poor prognosis in esophageal cancer patients.

Conclusions:

• PSMD14 acts as a deubiquitinating enzyme regulating SNAIL stability at the post-translational level.
• PSMD14 plays a crucial role in promoting esophageal cancer metastasis.
• PSMD14 represents a promising therapeutic target for combating tumor metastasis in esophageal cancer.