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USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534253/ https://www.ncbi.nlm.nih.gov/pubmed/34685632 http://dx.doi.org/10.3390/cells10102652 |
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author | Prieto-Garcia, Cristian Tomašković, Ines Shah, Varun Jayeshkumar Dikic, Ivan Diefenbacher, Markus |
author_facet | Prieto-Garcia, Cristian Tomašković, Ines Shah, Varun Jayeshkumar Dikic, Ivan Diefenbacher, Markus |
author_sort | Prieto-Garcia, Cristian |
collection | PubMed |
description | 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 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. |
format | Online Article Text |
id | pubmed-8534253 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85342532021-10-23 USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma Prieto-Garcia, Cristian Tomašković, Ines Shah, Varun Jayeshkumar Dikic, Ivan Diefenbacher, Markus Cells Review 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 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. MDPI 2021-10-04 /pmc/articles/PMC8534253/ /pubmed/34685632 http://dx.doi.org/10.3390/cells10102652 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Prieto-Garcia, Cristian Tomašković, Ines Shah, Varun Jayeshkumar Dikic, Ivan Diefenbacher, Markus USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma |
title | USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma |
title_full | USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma |
title_fullStr | USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma |
title_full_unstemmed | USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma |
title_short | USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma |
title_sort | usp28: oncogene or tumor suppressor? a unifying paradigm for squamous cell carcinoma |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534253/ https://www.ncbi.nlm.nih.gov/pubmed/34685632 http://dx.doi.org/10.3390/cells10102652 |
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