USP37 Promotes Lung Cancer Cell Migration by Stabilizing Snail Protein via Deubiquitination

Jiali Cai; Mengying Li; Xiang Wang; Lei Li; Qi Li; Zhaoyuan Hou; Hao Jia; Shiyuan Liu

doi:10.3389/fgene.2019.01324

USP37 Promotes Lung Cancer Cell Migration by Stabilizing Snail Protein via Deubiquitination

Front Genet. 2020 Jan 10:10:1324. doi: 10.3389/fgene.2019.01324. eCollection 2019.

Authors

Jiali Cai¹, Mengying Li², Xiang Wang¹, Lei Li³, Qi Li², Zhaoyuan Hou^{2

3

4}, Hao Jia^{2

4}, Shiyuan Liu¹

Affiliations

¹ Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
² Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.
³ Department of Thoracic Surgery, Lanling People's Hospital, Lanling County, Linyi, China.
⁴ Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry & Molecular Cellular Biology, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract

Snail is a prominent epithelial-mesenchymal transition (EMT) transcription factor and promotes metastasis. However, Snail protein is unstable and is quickly degraded through ubiquitination-mediated proteasome pathway. Deubiquitinases prevent Snail degradation by regulating the ubiquitination-mediated hydrolysis process. Our studies demonstrate that a deubiquitinating enzyme (DUB) family member, USP37, can deubiquitinate Snail and prevent degradation of Snail. USP37 is co-localized with Snail in the nucleus. Biologically, upregulated expression of USP37 promotes lung cancer cell migration, while depletion of Snail abolishes the effect of USP37. These data demonstrate that USP37 is a Snail-specific deubiquitinase and also indicate a potential therapeutic target for metastasis.

Keywords: Snail; USP37; cell migration; deubiquitination; lung cancer.