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Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancer
MKK3 is a member of the dual specificity kinase group specific upstream activator of p38 MAPK proteins. We originally identified MKK3 as mutant p53 (mutp53) gain-of-function (GOF) upregulated target gene in different tumor models. To deeply investigate the MKK3 functions in cancer, taking advantage...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935053/ https://www.ncbi.nlm.nih.gov/pubmed/31881903 http://dx.doi.org/10.1186/s13046-019-1513-4 |
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author | Stramucci, Lorenzo Bossi, Gianluca |
author_facet | Stramucci, Lorenzo Bossi, Gianluca |
author_sort | Stramucci, Lorenzo |
collection | PubMed |
description | MKK3 is a member of the dual specificity kinase group specific upstream activator of p38 MAPK proteins. We originally identified MKK3 as mutant p53 (mutp53) gain-of-function (GOF) upregulated target gene in different tumor models. To deeply investigate the MKK3 functions in cancer, taking advantage of a panel of authenticated colorectal cancer (CRC) lines and primary colonocytes, we found that MKK3 activates specifically p38delta MAPK protein, which signaling is further triggered by 5-fluorouracil (5-FU) treatments, a largely adopted chemotherapeutic drug in CRC clinical practice. The overall achieved results proposed the MKK3/p38delta MAPK as relevant molecular axis involved in abrogating efficacy to 5-FU treatments in CRC. This commentary will provide an overall discussion of the results that have been achieved contextualizing them in the overview of the knowledge in the p38 MAPK field in cancer disease. |
format | Online Article Text |
id | pubmed-6935053 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69350532019-12-30 Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancer Stramucci, Lorenzo Bossi, Gianluca J Exp Clin Cancer Res Commentary MKK3 is a member of the dual specificity kinase group specific upstream activator of p38 MAPK proteins. We originally identified MKK3 as mutant p53 (mutp53) gain-of-function (GOF) upregulated target gene in different tumor models. To deeply investigate the MKK3 functions in cancer, taking advantage of a panel of authenticated colorectal cancer (CRC) lines and primary colonocytes, we found that MKK3 activates specifically p38delta MAPK protein, which signaling is further triggered by 5-fluorouracil (5-FU) treatments, a largely adopted chemotherapeutic drug in CRC clinical practice. The overall achieved results proposed the MKK3/p38delta MAPK as relevant molecular axis involved in abrogating efficacy to 5-FU treatments in CRC. This commentary will provide an overall discussion of the results that have been achieved contextualizing them in the overview of the knowledge in the p38 MAPK field in cancer disease. BioMed Central 2019-12-27 /pmc/articles/PMC6935053/ /pubmed/31881903 http://dx.doi.org/10.1186/s13046-019-1513-4 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Commentary Stramucci, Lorenzo Bossi, Gianluca Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancer |
title | Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancer |
title_full | Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancer |
title_fullStr | Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancer |
title_full_unstemmed | Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancer |
title_short | Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancer |
title_sort | approaching the challenges of mkk3/p38delta mapk targeting for therapeutic purpose in colorectal cancer |
topic | Commentary |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935053/ https://www.ncbi.nlm.nih.gov/pubmed/31881903 http://dx.doi.org/10.1186/s13046-019-1513-4 |
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