Elevated expression levels of the protein kinase DYRK1B induce mesenchymal features in A549 lung cancer cells.
Humans
Dyrk Kinases
Protein Serine-Threonine Kinases
/ metabolism
Protein-Tyrosine Kinases
/ metabolism
Epithelial-Mesenchymal Transition
/ genetics
Lung Neoplasms
/ pathology
A549 Cells
Gene Expression Regulation, Neoplastic
Cell Movement
/ genetics
Adenocarcinoma
/ pathology
Snail Family Transcription Factors
/ metabolism
Cell Line, Tumor
Cell Proliferation
Adenocarcinoma of Lung
/ pathology
A549
Cancer cell migration
DYRK1B
Lung adenocarcinoma
Phenotypic plasticity
Protein kinase
Stress fibers
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
31 Oct 2024
31 Oct 2024
Historique:
received:
07
05
2024
accepted:
11
10
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
1
11
2024
Statut:
epublish
Résumé
The protein kinase DYRK1B is a negative regulator of cell proliferation but has been found to be overexpressed in diverse human solid cancers. While DYRK1B is recognized to promote cell survival and adaption to stressful conditions, the consequences of elevated DYRK1B levels in cancer cells are largely uncharted. To elucidate the role of DYRK1B in cancer cells, we established a A549 lung adenocarcinoma cell model featuring conditional overexpression of DYRK1B. This system was used to characterize the impact of heightened DYRK1B levels on gene expression and to monitor phenotypic and functional changes. A549 cells with induced overexpression of wild type DYRK1B acquired a mesenchymal cell morphology with diminished cell-cell contacts and a reorganization of the pericellular actin cytoskeleton into stress fibers. This transition was not observed in cells overexpressing a catalytically impaired DYRK1B variant. The phenotypic changes were associated with increased expression of the transcription factors SNAIL and SLUG, which are core regulators of epithelial mesenchymal transition (EMT). Further profiling of DYRK1B-overexpressing cells revealed transcriptional changes that are characteristic for the mesenchymal conversion of epithelial cells, including the upregulation of genes that are related to cancer cell invasion and metastasis. Functionally, DYRK1B overexpression enhanced the migratory capacity of A549 cells in a wound healing assay. The present data identify DYRK1B as a regulator of phenotypic plasticity in A549 cells. Increased expression of DYRK1B induces mesenchymal traits in A549 lung adenocarcinoma cells.
Sections du résumé
BACKGROUND
BACKGROUND
The protein kinase DYRK1B is a negative regulator of cell proliferation but has been found to be overexpressed in diverse human solid cancers. While DYRK1B is recognized to promote cell survival and adaption to stressful conditions, the consequences of elevated DYRK1B levels in cancer cells are largely uncharted.
METHODS
METHODS
To elucidate the role of DYRK1B in cancer cells, we established a A549 lung adenocarcinoma cell model featuring conditional overexpression of DYRK1B. This system was used to characterize the impact of heightened DYRK1B levels on gene expression and to monitor phenotypic and functional changes.
RESULTS
RESULTS
A549 cells with induced overexpression of wild type DYRK1B acquired a mesenchymal cell morphology with diminished cell-cell contacts and a reorganization of the pericellular actin cytoskeleton into stress fibers. This transition was not observed in cells overexpressing a catalytically impaired DYRK1B variant. The phenotypic changes were associated with increased expression of the transcription factors SNAIL and SLUG, which are core regulators of epithelial mesenchymal transition (EMT). Further profiling of DYRK1B-overexpressing cells revealed transcriptional changes that are characteristic for the mesenchymal conversion of epithelial cells, including the upregulation of genes that are related to cancer cell invasion and metastasis. Functionally, DYRK1B overexpression enhanced the migratory capacity of A549 cells in a wound healing assay.
CONCLUSIONS
CONCLUSIONS
The present data identify DYRK1B as a regulator of phenotypic plasticity in A549 cells. Increased expression of DYRK1B induces mesenchymal traits in A549 lung adenocarcinoma cells.
Identifiants
pubmed: 39482615
doi: 10.1186/s12885-024-13057-0
pii: 10.1186/s12885-024-13057-0
doi:
Substances chimiques
Dyrk Kinases
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Protein-Tyrosine Kinases
EC 2.7.10.1
Snail Family Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1341Informations de copyright
© 2024. The Author(s).
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