ERK2 signaling regulates cell-cell adhesion of epithelial cells and enhances growth factor-induced cell scattering
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F22%3A00565487" target="_blank" >RIV/61388971:_____/22:00565487 - isvavai.cz</a>
Alternative codes found
RIV/68378050:_____/22:00565487 RIV/00216208:11310/22:10456643
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0898656822001930?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0898656822001930?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.cellsig.2022.110431" target="_blank" >10.1016/j.cellsig.2022.110431</a>
Alternative languages
Result language
angličtina
Original language name
ERK2 signaling regulates cell-cell adhesion of epithelial cells and enhances growth factor-induced cell scattering
Original language description
The ERK signaling pathway, consisting of core protein kinases Raf, MEK and effector kinases ERK1/2, regulates various biological outcomes such as cell proliferation, differentiation, apoptosis, or cell migration. Signal transduction through the ERK signaling pathway is tightly controlled at all levels of the pathway. However, it is not well understood whether ERK pathway signaling can be modulated by the abundance of ERK pathway core kinases. In this study, we investigated the effects of low-level overexpression of the ERK2 isoform on the phenotype and scattering of cuboidal MDCK epithelial cells growing in discrete multicellular clusters. We show that ERK2 overexpression reduced the vertical size of lateral membranes that contain cell-cell adhesion complexes. Consequently, ERK2 overexpressing cells were unable to develop cuboidal shape, remained flat with increased spread area and intercellular adhesive contacts were present only on the basal side. Interestingly, ERK2 overexpression was not sufficient to increase phosphorylation of multiple downstream targets including transcription factors and induce global changes in gene expression, namely to increase the expression of pro-migratory transcription factor Fra1. However, ERK2 overexpression enhanced HGF/SF-induced cell scattering as these cells scattered more rapidly and to a greater extent than parental cells. Our results suggest that an increase in ERK2 expression primarily reduces cell-cell cohesion and that weakened intercellular adhesion synergizes with upstream signaling in the conversion of the multicellular epithelium into single migrating cells. This mechanism may be clinically relevant as the analysis of clinical data revealed that in one type of cancer, pancreatic adenocarcinoma, ERK2 overexpression correlates with a worse prognosis.
Czech name
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Czech description
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Classification
Type
J<sub>SC</sub> - Article in a specialist periodical, which is included in the SCOPUS database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cellular Signalling
ISSN
0898-6568
e-ISSN
1873-3913
Volume of the periodical
99
Issue of the periodical within the volume
November 2022
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
110431
UT code for WoS article
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EID of the result in the Scopus database
2-s2.0-85137085967