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

The epithelial-mesenchymal transition (EMT) transcription factor SNAIL is associated with distant metastasis and poor prognosis of esophageal squamous cell carcinoma (ESCC) patients. The proteolysis of SNAIL is mediated by the ubiquitin-proteasome system. Several E3 ligases have been characterized t...

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Bibliographic Details
Published in:Cancer letters 2018-04, Vol.418, p.125-134
Main Authors: Zhu, Rui, Liu, Yongshuo, Zhou, Honghong, Li, Lei, Li, Yi, Ding, Fang, Cao, Xiufeng, Liu, Zhihua
Format: Article
Language:English
Subjects:
Apoptosis
Cell migration
Deubiquitination
Enzymes
Esophageal cancer
Esophageal squamous cell carcinoma
Esophagus
Immunoglobulins
Lung cancer
Mass spectrometry
Mass spectroscopy
Medical prognosis
Mesenchyme
Metastases
Metastasis
Plasmids
Post-translation
Prognosis
Proteasomes
Proteins
Proteolysis
PSMD14
Scientific imaging
SNAIL
Snail protein
Squamous cell carcinoma
Transcription factors
Tumor metastasis
Tumorigenesis
Ubiquitin
Ubiquitin-protein ligase
Ubiquitination
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Summary:The epithelial-mesenchymal transition (EMT) transcription factor SNAIL is associated with distant metastasis and poor prognosis of esophageal squamous cell carcinoma (ESCC) patients. The proteolysis of SNAIL is mediated by the ubiquitin-proteasome system. Several E3 ligases have been characterized to promote SNAIL ubiquitination and degradation. However, the reverse process – deubiquitination of SNAIL remains largely unknown. In this study, we performed a mass spectrometry to examine the interaction between SNAIL and deubiquitinating enzyme(s). Subsequently, the deubiquitinating enzyme PSMD14 was identified to target SNAIL for deubiquitination and stabilization. Furthermore, knockdown of PSMD14 significantly blocks SNAIL-induced EMT and then suppresses tumor cell migration and invasion in vitro and tumor metastasis in vivo. In addition, the high expression level of PSMD14 predicts poor prognosis for esophageal cancer patients. These findings suggest PSMD14 as a bona fide deubiquitinating enzyme to regulate SNAIL at the post-translational level and provide a promising therapeutic strategy against tumor metastasis of esophageal cancer. •PSMD14 is a novel deubiquitinating enzyme to regulate SNAIL stability.•PSMD14 knockdown inhibits SNAIL-induced EMT process and tumor metastasis.•High PSMD14 level predicts poor survival outcomes in esophageal cancer patients.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2018.01.025