Loss of ubiquitin-specific peptidase 18 destabilizes 14-3-3ζ protein and represses lung cancer metastasis

• Published in: Cancer biology & therapy 2022-12, Vol.23 (1), p.265-280
• Main Authors: Chen, Zibo, Zheng, Lin, Chen, Yulong, Liu, Xiuxia, Kawakami, Masanori, Mustachio, Lisa Maria, Roszik, Jason, Ferry-Galow, Katherine V., Parchment, Ralph E., Liu, Xin, Andresson, Thorkell, Duncan, Gerard, Kurie, Jonathan M., Rodriguez-Canales, Jaime, Liu, Xi, Dmitrovsky, Ethan
• Format: Article
• Language: English
• Subjects: 14-3-3 Proteins - genetics; 14-3-3 Proteins - metabolism; 14-3-3ζ; Adenocarcinoma of Lung; Animals; Deubiquitinase; Humans; lung cancer and metastasis; Lung Neoplasms - pathology; Mice; Research Paper; Ubiquitin Thiolesterase - genetics; Ubiquitin Thiolesterase - metabolism; Ubiquitin-Specific Proteases - metabolism; USP18
• ISSN: 1538-4047; 1555-8576
• DOI: 10.1080/15384047.2022.2054242

Cancer metastasis is a major cause of cancer-related mortality. Strategies to reduce metastases are needed especially in lung cancer, the most common cause of cancer mortality. We previously reported increased ubiquitin-specific peptidase 18 (USP18) expression in lung and other cancers. Engineered reduction of USP18 expression repressed lung cancer growth and promoted apoptosis. This deubiquitinase (DUB) stabilized targeted proteins by removing the complex interferon-stimulated gene 15 (ISG15). This study explores if the loss of USP18 reduced lung cancer metastasis. USP18 knock-down in lung cancer cells was independently achieved using small hairpin RNAs (shRNAs) and small interfering RNAs (siRNAs). USP18 knock-down reduced lung cancer growth, wound-healing, migration, and invasion versus controls (P