| First Author | Richter K | Year | 2018 |
| Journal | Mol Cancer Res | Volume | 16 |
| Issue | 6 | Pages | 1000-1012 |
| PubMed ID | 29545478 | Mgi Jnum | J:262372 |
| Mgi Id | MGI:6159554 | Doi | 10.1158/1541-7786.MCR-17-0452 |
| Citation | Richter K, et al. (2018) USP28 Deficiency Promotes Breast and Liver Carcinogenesis as well as Tumor Angiogenesis in a HIF-independent Manner. Mol Cancer Res 16(6):1000-1012 |
| abstractText | 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-1alpha, p53, and 53BP1.Implications: 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. Mol Cancer Res; 16(6); 1000-12. (c)2018 AACR. |
