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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...

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Autores principales: Prieto-Garcia, Cristian, Tomašković, Ines, Shah, Varun Jayeshkumar, Dikic, Ivan, Diefenbacher, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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