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 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.

Zhu R ，Liu Y ，Zhou H ，Li L ，Li Y ，Ding F ，Cao X ，Liu Z ... -  《-》

The PSMD14 inhibitor Thiolutin as a novel therapeutic approach for esophageal squamous cell carcinoma through facilitating SNAIL degradation.

Jing C ，Li X ，Zhou M ，Zhang S ，Lai Q ，Liu D ，Ye B ，Li L ，Wu Y ，Li H ，Yue K ，Chen P ，Yao X ，Wu Y ，Duan Y ，Wang X ... -  《Theranostics》

USP26 promotes esophageal squamous cell carcinoma metastasis through stabilizing Snail.

Snail is an important transcription factor of epithelial-mesenchymal transition (EMT) and related to poor prognosis and distant metastasis of tumor patients. Snail is a liable protein and degraded by ubiquitin-proteasome system. There are various E3 ligases mediating its degradation, but the deubiquitinating enzyme reversed Snail degradation is not fully understood. In this study, we screened a DUB library and found USP26 is a potent deubiquitinase mediating Snail stabilization. We also identified that USP26 is a booster of esophageal squamous cell carcinoma (ESCC) cell migration and invasion, and it is highly expressed in ESCC samples. Our observation demonstrates that USP26 is a novel deubiquitinating enzyme of Snail and it provides a potential target for the therapy of esophageal cancer metastasis.

Li L ，Zhou H ，Zhu R ，Liu Z ... -  《-》

EIF3H promotes aggressiveness of esophageal squamous cell carcinoma by modulating Snail stability.

Guo X ，Zhu R ，Luo A ，Zhou H ，Ding F ，Yang H ，Liu Z ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

CBX8 Suppresses Tumor Metastasis via Repressing Snail in Esophageal Squamous Cell Carcinoma.

Wang G ，Tang J ，Zhan W ，Zhang R ，Zhang M ，Liao D ，Wang X ，Wu Y ，Kang T ... -  《-》