1. Loss of ubiquitin-specific peptidase 18 destabilizes 14-3-3ζ protein and represses lung cancer metastasis
- Author
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Zibo Chen, Lin Zheng, Yulong Chen, Xiuxia Liu, Masanori Kawakami, Lisa Maria Mustachio, Jason Roszik, Katherine V. Ferry-Galow, Ralph E. Parchment, Xin Liu, Thorkell Andresson, Gerard Duncan, Jonathan M. Kurie, Jaime Rodriguez-Canales, Xi Liu, and Ethan Dmitrovsky
- Subjects
deubiquitinase ,usp18 ,14-3-3ζ ,lung cancer and metastasis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
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
- Published
- 2022
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