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UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis
The leading cause of cutaneous squamous cell carcinomas (cSCCs) is exposure to ultraviolet radiation (UV). Unlike most other cancers, the incidence rates of cSCCs are still on the rise and the treatment options currently available are limited. We have recently found that dihydroorotate dehydrogenase...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760220/ https://www.ncbi.nlm.nih.gov/pubmed/31551419 http://dx.doi.org/10.1038/s41389-019-0161-z |
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author | Hosseini, Mohsen Dousset, Léa Michon, Pauline Mahfouf, Walid Muzotte, Elodie Bergeron, Vanessa Bortolotto, Doriane Rossignol, Rodrigue Moisan, François Taieb, Alain Bouzier-Sore, Anne-Karine Rezvani, Hamid R. |
author_facet | Hosseini, Mohsen Dousset, Léa Michon, Pauline Mahfouf, Walid Muzotte, Elodie Bergeron, Vanessa Bortolotto, Doriane Rossignol, Rodrigue Moisan, François Taieb, Alain Bouzier-Sore, Anne-Karine Rezvani, Hamid R. |
author_sort | Hosseini, Mohsen |
collection | PubMed |
description | The leading cause of cutaneous squamous cell carcinomas (cSCCs) is exposure to ultraviolet radiation (UV). Unlike most other cancers, the incidence rates of cSCCs are still on the rise and the treatment options currently available are limited. We have recently found that dihydroorotate dehydrogenase (DHODH), which is the rate-limiting enzyme in the de novo pyrimidine synthesis pathway, plays a critical role in UVB-induced energy metabolism reprogramming. Using a multistage model of UVB radiation-induced skin cancer, we show that UVB-induced DHODH upregulation is mainly regulated transcriptionally by STAT3. Our results indicate that chronic inhibition of DHODH by leflunomide (LFN) blocks UVB-induced tumor initiation. Human tumor xenograft studies showed that LFN treatment reduces growth of established tumors when used in combination with a genotoxic agent, 5-fluorouracil (5-FU). Our data suggest that DHODH is a promising target for chemoprevention and combination therapy of UVB-induced cSCCs. |
format | Online Article Text |
id | pubmed-6760220 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67602202019-09-27 UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis Hosseini, Mohsen Dousset, Léa Michon, Pauline Mahfouf, Walid Muzotte, Elodie Bergeron, Vanessa Bortolotto, Doriane Rossignol, Rodrigue Moisan, François Taieb, Alain Bouzier-Sore, Anne-Karine Rezvani, Hamid R. Oncogenesis Article The leading cause of cutaneous squamous cell carcinomas (cSCCs) is exposure to ultraviolet radiation (UV). Unlike most other cancers, the incidence rates of cSCCs are still on the rise and the treatment options currently available are limited. We have recently found that dihydroorotate dehydrogenase (DHODH), which is the rate-limiting enzyme in the de novo pyrimidine synthesis pathway, plays a critical role in UVB-induced energy metabolism reprogramming. Using a multistage model of UVB radiation-induced skin cancer, we show that UVB-induced DHODH upregulation is mainly regulated transcriptionally by STAT3. Our results indicate that chronic inhibition of DHODH by leflunomide (LFN) blocks UVB-induced tumor initiation. Human tumor xenograft studies showed that LFN treatment reduces growth of established tumors when used in combination with a genotoxic agent, 5-fluorouracil (5-FU). Our data suggest that DHODH is a promising target for chemoprevention and combination therapy of UVB-induced cSCCs. Nature Publishing Group UK 2019-09-24 /pmc/articles/PMC6760220/ /pubmed/31551419 http://dx.doi.org/10.1038/s41389-019-0161-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hosseini, Mohsen Dousset, Léa Michon, Pauline Mahfouf, Walid Muzotte, Elodie Bergeron, Vanessa Bortolotto, Doriane Rossignol, Rodrigue Moisan, François Taieb, Alain Bouzier-Sore, Anne-Karine Rezvani, Hamid R. UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis |
title | UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis |
title_full | UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis |
title_fullStr | UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis |
title_full_unstemmed | UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis |
title_short | UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis |
title_sort | uvb-induced dhodh upregulation, which is driven by stat3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760220/ https://www.ncbi.nlm.nih.gov/pubmed/31551419 http://dx.doi.org/10.1038/s41389-019-0161-z |
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