USP18 通过去泛素化 PLK1 促进头颈部鳞状细胞癌的增殖、侵袭和迁移

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2024-10-01 DOI:10.1016/j.yexcr.2024.114284

Liang Geng , Fangfang Liu , Liyun Yang , Yan Liu , Geping Wu

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引用次数: 0

摘要

泛素特异性肽酶 18（USP18）是一种成熟的去泛素化酶，已被广泛认为与多种人类肿瘤的恶性发展有关。然而，它在头颈部鳞状细胞癌（HNSC）中的作用还需要进一步研究。在这里，我们发现 USP18 在 HNSC 中显著上调，敲除 USP18 能明显抑制肿瘤在体内的生长。此外，沉默 USP18 可减轻 HNSC 细胞的增殖、侵袭和迁移，而过表达 USP18 则会产生相反的效果。从机理上讲，USP18通过其去泛素化酶活性，减少了与K48相连的多聚样激酶1（PLK1）泛素化，从而稳定了该蛋白。随后，我们验证了 USP18 可调节 PLK1 以激活 mTORC1 通路，从而促进 HNSC 细胞的增殖、侵袭和迁移。总之，我们的研究结果表明，USP18 在 HNSC 细胞中的高表达可通过调节 PLK1-mTORC1 通路促进肿瘤发生。

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USP18 promotes the proliferation, invasion, and migration of head and neck squamous cell carcinoma by deubiquitinating PLK1

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.

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.