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USP28: oncogene or tumor suppressor? a unifying paradigm for squamous cell carcinoma

Please always quote using this URN: urn:nbn:de:bvb:20-opus-248409
  • Squamous cell carcinomas are therapeutically challenging tumor entities. Low response rates to radiotherapy and chemotherapy are commonly observed in squamous patients and, accordingly, the mortality rate is relatively high compared to other tumor entities. Recently, targeting USP28 has been emerged as a potential alternative to improve the therapeutic response and clinical outcomes of squamous patients. USP28 is a catalytically active deubiquitinase that governs a plethora of biological processes, including cellular proliferation, DNA damageSquamous cell carcinomas are therapeutically challenging tumor entities. Low response rates to radiotherapy and chemotherapy are commonly observed in squamous patients and, accordingly, the mortality rate is relatively high compared to other tumor entities. Recently, targeting USP28 has been emerged as a potential alternative to improve the therapeutic response and clinical outcomes of squamous patients. USP28 is a catalytically active deubiquitinase that governs a plethora of biological processes, including cellular proliferation, DNA damage repair, apoptosis and oncogenesis. In squamous cell carcinoma, USP28 is strongly expressed and stabilizes the essential squamous transcription factor ΔNp63, together with important oncogenic factors, such as NOTCH1, c-MYC and c-JUN. It is presumed that USP28 is an oncoprotein; however, recent data suggest that the deubiquitinase also has an antineoplastic effect regulating important tumor suppressor proteins, such as p53 and CHK2. In this review, we discuss: (1) The emerging role of USP28 in cancer. (2) The complexity and mutational landscape of squamous tumors. (3) The genetic alterations and cellular pathways that determine the function of USP28 in squamous cancer. (4) The development and current state of novel USP28 inhibitors.show moreshow less

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Metadaten
Author: Cristian Prieto-Garcia, Ines Tomašković, Varun Jayeshkumar Shah, Ivan Dikic, Markus Diefenbacher
URN:urn:nbn:de:bvb:20-opus-248409
Document Type:Journal article
Faculties:Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften
Medizinische Fakultät / Comprehensive Cancer Center Mainfranken
Language:English
Parent Title (English):Cells
ISSN:2073-4409
Year of Completion:2021
Volume:10
Issue:10
Article Number:2652
Source:Cells (2021) 10:10, 2652. https://doi.org/10.3390/cells10102652
DOI:https://doi.org/10.3390/cells10102652
Sonstige beteiligte Institutionen:Mildred Scheel Early Career Center
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:DUB inhibitor; FBXW7; SCC; Tp63; USP25; USP28; c-MYC; cancer; p53; squamous; ΔNp63
Release Date:2022/11/24
Date of first Publication:2021/10/04
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International