PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer.
Life Sci Alliance
; 6(10)2023 10.
Article
em En
| MEDLINE
| ID: mdl-37536978
ABSTRACT
Triple-negative breast cancers (TNBCs) are the most aggressive breast cancers, and therapeutic options mainly rely on chemotherapy and immunotherapy. Although synthetic glucocorticoids (GCs) are given to alleviate the side effects of these treatments, GCs and their receptor, the glucocorticoid receptor (GR), were recently associated with detrimental effects, albeit the mechanisms involved remain elusive. Here, we identified the arginine methyltransferase PRMT5 as a master coregulator of GR, serving as a scaffold protein to recruit phospho-HP1γ and subsequently RNA polymerase II, independently of its methyltransferase activity. Moreover, the GR/PRMT5/HP1γ complex regulated the transcription of GC-target genes involved in cell motility and triggering cell migration of human TNBC cells in vitro and in a zebrafish model. Of note, we observed that GR/PRMT5 interaction was low in primary tumors but significantly increased in residual tumors treated with chemotherapy and GCs in neoadjuvant setting. These data suggest that the routine premedication prescription of GCs for early TNBC patients should be further assessed and that this complex could potentially be modulated to specifically target deleterious GR effects.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína-Arginina N-Metiltransferases
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Movimento Celular
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Neoplasias de Mama Triplo Negativas
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Glucocorticoides
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article