AGR2 oncoprotein inhibits p38MAPK and p53 activation through a DUSP10-mediated regulatory pathway

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F16%3AN0000004" target="_blank" >RIV/00209805:_____/16:N0000004 - isvavai.cz</a>

Result on the web

<a href="http://www.sciencedirect.com/science/article/pii/S1574789115002392" target="_blank" >http://www.sciencedirect.com/science/article/pii/S1574789115002392</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.molonc.2015.12.003" target="_blank" >10.1016/j.molonc.2015.12.003</a>

Result language

angličtina

Original language name

AGR2 oncoprotein inhibits p38MAPK and p53 activation through a DUSP10-mediated regulatory pathway

Original language description

The tumor suppressor p53 plays a key role in malignant transformation and tumor development. However, the frequency of p53 mutations within individual types of cancer is different, suggesting the existence of other mechanisms attenuating p53 tumor suppressor activity. Changes in upstream regulators of p53 such as MDM2 amplification and overexpression, expression of viral oncoproteins, estrogen receptor signaling, or ganges in p53 transcriptional target genes were previously described in wild-type p53 tumors. We identified a novel pathway responsible for attenuation of p53 activity in human cancers. We demonstrate that AGR2, which is overexpressed in a variety of human cancers and provides a poor prognosis, up-regulates DUSP10 which subsequently inhibits p38 MAPK and prevents p53 activation by phosphorylation. Analysis of human breast cancers reveals that AGR2 specifically provides a poor prognosis in ERþ breast cancers with wildtype p53 but not ER- or mutant p53 breast cancers, and analysis of independent data sets show that DUSP10 levels also have prognostic significance in this specific sub-group of patients. These data not only reveal a novel pro-oncogenic signaling pathway mediating resistance to DNA damaging agents in human tumors, but also has implications for designing alternative strategies for modulation of wild-type p53 activity in cancer therapy.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Oncology

ISSN

1574-7891

e-ISSN

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Volume of the periodical

10

Issue of the periodical within the volume

5

Country of publishing house

GB - UNITED KINGDOM

Number of pages

11

Pages from-to

652-662

UT code for WoS article

000377310800002

EID of the result in the Scopus database

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