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OTUB1 promotes esophageal squamous cell carcinoma metastasis through modulating Snail stability

Abstract

Snail is a key regulator of epithelial–mesenchymal transition (EMT) and plays an important role in tumor progression and metastasis. Snail is rapidly degraded in the cells and its protein level is critically controlled. Although several E3 ligases regulating Snail degradation have been defined, the deubiquitinases (DUBs) responsible for Snail deubiquitination are less studied. We identified ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1) as a DUB that stabilizes Snail through preventing its ubiquitination and proteasomal degradation. Functionally, OTUB1 facilitates metastasis of esophageal squamous cell carcinoma (ESCC) through promoting Snail protein stability. Moreover, OTUB1 is highly expressed in ESCC and higher expression of OTUB1 predicts poor prognosis. These findings suggest that OTUB1 is an essential regulator of Snail and plays a critical role in facilitating esophageal cancer progression.

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Acknowledgements

This work was supported by National Key R&D Program of China (2016YFC1302100), National Science Foundation of China (81420108025), and CAMS Initiative for Innovative Medicine (2016-I2M-1-001). We thank Dr. Shimada Y. (Kyoto University, Kyoto, Japan) for kindly providing the ESCC cell lines.

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Correspondence to Zhihua Liu.

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We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work.

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These authors contributed equally: Honghong Zhou, Yongshuo Liu, and Rui Zhu.

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Zhou, H., Liu, Y., Zhu, R. et al. OTUB1 promotes esophageal squamous cell carcinoma metastasis through modulating Snail stability. Oncogene 37, 3356–3368 (2018). https://doi.org/10.1038/s41388-018-0224-1

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