Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancer
Abstract 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 a...
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doaj-9cf277f638ad46eabeaf84c3f038a59c2020-12-27T12:02:41ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-12-013811310.1186/s13046-019-1513-4Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancerLorenzo Stramucci0Gianluca Bossi1Oncogenomic and Epigenetic Unit, Department of Diagnostic Research and Technological Innovation, IRCCS - Regina Elena National Cancer InstituteOncogenomic and Epigenetic Unit, Department of Diagnostic Research and Technological Innovation, IRCCS - Regina Elena National Cancer InstituteAbstract 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.https://doi.org/10.1186/s13046-019-1513-4Colorectal CancerMKK3 / p38 MAPK signallingp38 delta MAPKChemotherapyTarget therapyCombined treatments |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lorenzo Stramucci Gianluca Bossi |
spellingShingle |
Lorenzo Stramucci Gianluca Bossi Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancer Journal of Experimental & Clinical Cancer Research Colorectal Cancer MKK3 / p38 MAPK signalling p38 delta MAPK Chemotherapy Target therapy Combined treatments |
author_facet |
Lorenzo Stramucci Gianluca Bossi |
author_sort |
Lorenzo Stramucci |
title |
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_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_sort |
approaching the challenges of mkk3/p38delta mapk targeting for therapeutic purpose in colorectal cancer |
publisher |
BMC |
series |
Journal of Experimental & Clinical Cancer Research |
issn |
1756-9966 |
publishDate |
2019-12-01 |
description |
Abstract 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. |
topic |
Colorectal Cancer MKK3 / p38 MAPK signalling p38 delta MAPK Chemotherapy Target therapy Combined treatments |
url |
https://doi.org/10.1186/s13046-019-1513-4 |
work_keys_str_mv |
AT lorenzostramucci approachingthechallengesofmkk3p38deltamapktargetingfortherapeuticpurposeincolorectalcancer AT gianlucabossi approachingthechallengesofmkk3p38deltamapktargetingfortherapeuticpurposeincolorectalcancer |
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