Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
Biocenter Oulu, University of Oulu, Oulu, Finland.
Mol Cancer Res. 2018 Jun;16(6):1000-1012. doi: 10.1158/1541-7786.MCR-17-0452. Epub 2018 Mar 15.
Recent studies suggest that the ubiquitin-specific protease USP28 plays an important role in cellular repair and tissue remodeling, which implies that it has a direct role in carcinogenesis. The carcinogenic potential of USP28 was investigated in a comprehensive manner using patients, animal models, and cell culture. The findings demonstrate that overexpression of USP28 correlates with a better survival in patients with invasive ductal breast carcinoma. Mouse xenograft experiments with USP28-deficient breast cancer cells also support this view. Furthermore, lack of USP28 promotes a more malignant state of breast cancer cells, indicated by an epithelial-to-mesenchymal (EMT) transition, elevated proliferation, migration, and angiogenesis as well as a decreased adhesion. In addition to breast cancer, lack of USP28 in mice promoted an earlier onset and a more severe tumor formation in a chemical-induced liver cancer model. Mechanistically, the angio- and carcinogenic processes driven by the lack of USP28 appeared to be independent of HIF-1α, p53, and 53BP1. The findings of this study are not limited to one particular type of cancer but are rather applicable for carcinogenesis in a more general manner. The obtained data support the view that USP28 is involved in tumor suppression and has the potential to be a prognostic marker. .
最近的研究表明，泛素特异性蛋白酶 USP28 在细胞修复和组织重塑中发挥着重要作用，这意味着它在致癌作用中具有直接作用。使用患者、动物模型和细胞培养物，全面研究了 USP28 的致癌潜力。研究结果表明，USP28 的过表达与浸润性导管乳腺癌患者的生存改善相关。USP28 缺陷的乳腺癌细胞的小鼠异种移植实验也支持这一观点。此外，缺乏 USP28 会促进乳腺癌细胞向更恶性的状态发展，表现为上皮间质转化（EMT）、增殖、迁移和血管生成增加，以及黏附减少。除乳腺癌外，缺乏 USP28 的小鼠在化学诱导的肝癌模型中促进了更早的发病和更严重的肿瘤形成。从机制上讲，USP28 缺乏驱动的血管生成和致癌过程似乎独立于 HIF-1α、p53 和 53BP1。本研究的结果不仅限于某一种癌症，而是更普遍地适用于癌症的发生。获得的数据支持 USP28 参与肿瘤抑制的观点，并有可能成为一种预后标志物。
