USP18 promotes the proliferation, invasion, and migration of head and neck squamous cell carcinoma by deubiquitinating PLK1
Liang Geng, Fangfang Liu, Liyun Yang, Yan Liu, Guang Wu
Abstract
The ubiquitin specific peptidase 18 (USP18), a well-established deubiquitinase, has been extensively implicated in the malignant progression of various human tumors. However, its role in head and neck squamous cell carcinoma (HNSC) requires further investigation. Here, we revealed that USP18 was significantly upregulated in HNSC and knockdown of USP18 markedly suppressed tumor growth in vivo. Furthermore, silencing USP18 attenuated HNSC cell proliferation, invasion, and migration, while overexpression of USP18 exerted converse effects. Mechanistically, USP18 diminished K48-linked ubiquitination of polo-like kinase 1 (PLK1) to stabilize the protein through its deubiquitinase activity. Subsequently, we validated that USP18 modulated PLK1 to activate the mTORC1 pathway, thereby facilitating HNSC cell proliferation, invasion, and migration. In conclusion, our findings demonstrate that elevated expression of USP18 in HNSC cells promotes tumorigenesis by regulating the PLK1-mTORC1 pathway. • Up-regulated USP18 facilitates the proliferation, invasion, and migration of HNSC cells. • USP18 enhances PLK1 protein stability through reducing its K48-linked polyubiquitination. • USP18-PLK1-mTORC1 axis governs the proliferation, invasion, and migration of HNSC cells.