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ERK2 signaling regulates cell-cell adhesion of epithelial cells and enhances growth factor-induced cell scattering
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SYSNO ASEP 0565487 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title ERK2 signaling regulates cell-cell adhesion of epithelial cells and enhances growth factor-induced cell scattering Author(s) Rasl, Jan (MBU-M) ORCID
Grušanović, Josipa (MBU-M)
Klímová, Zuzana (MBU-M) RID
Čáslavský, Josef (MBU-M)
Groušl, Tomáš (MBU-M) RID, ORCID
Novotný, Jiří (UMG-J) ORCID
Kolář, Michal (UMG-J) RID, ORCID
Vomastek, Tomáš (MBU-M) RID, ORCIDArticle number 110431 Source Title Cellular Signalling. - : Elsevier - ISSN 0898-6568
Roč. 99, November 2022 (2022)Number of pages 13 s. Language eng - English Country US - United States Keywords Cell scattering ; Cell-cell adhesions ; Epithelial plasticity ; erk ; Fra1 ; hgf/sf Subject RIV EE - Microbiology, Virology OECD category Cell biology Subject RIV - cooperation Institute of Molecular Genetics R&D Projects LM2018129 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF18_046/0016045 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GA18-11908S GA ČR - Czech Science Foundation (CSF) GA19-08013S GA ČR - Czech Science Foundation (CSF) EF16_019/0000785 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support MBU-M - RVO:61388971 ; UMG-J - RVO:68378050 UT WOS 001093387200001 EID SCOPUS 85137085967 DOI 10.1016/j.cellsig.2022.110431 Annotation 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. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2023 Electronic address https://www.sciencedirect.com/science/article/pii/S0898656822001930?via%3Dihub
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