Transcription factor activating enhancer-binding protein 2ε (AP2ε) modulates phenotypic plasticity and progression of malignant melanoma.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
21 May 2024
21 May 2024
Historique:
received:
22
12
2023
accepted:
08
05
2024
revised:
04
05
2024
medline:
22
5
2024
pubmed:
22
5
2024
entrez:
21
5
2024
Statut:
epublish
Résumé
Malignant melanoma, the most aggressive form of skin cancer, is often incurable once metastatic dissemination of cancer cells to distant organs has occurred. We investigated the role of Transcription Factor Activating Enhancer-Binding Protein 2ε (AP2ε) in the progression of metastatic melanoma. Here, we observed that AP2ε is a potent activator of metastasis and newly revealed AP2ε to be an important player in melanoma plasticity. High levels of AP2ε lead to worsened prognosis of melanoma patients. Using a transgenic melanoma mouse model with a specific loss of AP2ε expression, we confirmed the impact of AP2ε to modulate the dynamic switch from a migratory to a proliferative phenotype. AP2ε deficient melanoma cells show a severely reduced migratory potential in vitro and reduced metastatic behavior in vivo. Consistently, we revealed increased activity of AP2ε in quiescent and migratory cells compared to heterogeneously proliferating cells in bioprinted 3D models. In conclusion, these findings disclose a yet-unknown role of AP2ε in maintaining plasticity and migration in malignant melanoma cells.
Identifiants
pubmed: 38773108
doi: 10.1038/s41419-024-06733-3
pii: 10.1038/s41419-024-06733-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
351Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 429280966, subproject B12
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : TRR305, 429280966, subproject B12
Informations de copyright
© 2024. The Author(s).
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