BRD4L cooperates with MYC to block local tumor invasion via suppression of S100A10.
Cell Signal
; 119: 111173, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38604343
ABSTRACT
Targeted therapy based on BRD4 and MYC shows promise due to their well-researched oncogenic functions in cancer, but their tumor-suppressive roles are less understood. In this study, we employ a systematic approach to delete exons that encode the low-complexity domain (LCD) of BRD4L in cells by using CRISPR-Cas9. In particular, the deletion of exon 14 (BRD4-E14) results in cellular morphological changes towards spindle-shaped and loosely packed. BRD4-E14 deficient cells show increased cell migration and reduced cell adhesion. The expression of S100A10 was significantly increased in cells lacking E14. BRD4L binds with MYC via the E14-encoded region of the LCD to inhibit the expression of S100A10. In cancer tissues, there is a positive correlation between BRD4 and MYC, while both of these proteins are negatively associated with S100A10 expression. Finally, knocking out the BRD4-E14 region or MYC promotes tumor growth in vivo. Together, these data support a tumor-suppressive role of BRD4L and MYC in some contexts. This discovery emphasizes the significance of a discreetly design and precise patient recruitment in clinical trials that testing cancer therapy based BRD4 and MYC.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Proteínas S100
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Movimiento Celular
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Proteínas Proto-Oncogénicas c-myc
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Proteínas de Ciclo Celular
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cell Signal
Año:
2024
Tipo del documento:
Article
País de afiliación:
China