A systems-level analysis of the mutually antagonistic roles of RKIP and BACH1 in dynamics of cancer cell plasticity.
J R Soc Interface
; 20(208): 20230389, 2023 11.
Article
en En
| MEDLINE
| ID: mdl-37963558
ABSTRACT
Epithelial-mesenchymal transition (EMT) is an important axis of phenotypic plasticity-a hallmark of cancer metastasis. Raf kinase-B inhibitor protein (RKIP) and BTB and CNC homology 1 (BACH1) are reported to influence EMT. In breast cancer, they act antagonistically, but the exact nature of their roles in mediating EMT and associated other axes of plasticity remains unclear. Here, analysing transcriptomic data, we reveal their antagonistic trends in a pan-cancer manner in terms of association with EMT, metabolic reprogramming and immune evasion via PD-L1. Next, we developed and simulated a mechanism-based gene regulatory network that captures how RKIP and BACH1 engage in feedback loops with drivers of EMT and stemness. We found that RKIP and BACH1 belong to two antagonistic 'teams' of players-while BACH1 belonged to the one driving pro-EMT, stem-like and therapy-resistant cell states, RKIP belonged to the one enabling pro-epithelial, less stem-like and therapy-sensitive phenotypes. Finally, we observed that low RKIP levels and upregulated BACH1 levels associated with worse clinical outcomes in many cancer types. Together, our systems-level analysis indicates that the emergent dynamics of underlying regulatory network enable the antagonistic patterns of RKIP and BACH1 with various axes of cancer cell plasticity, and with patient survival data.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Proteínas de Unión a Fosfatidiletanolamina
Límite:
Female
/
Humans
Idioma:
En
Revista:
J R Soc Interface
Año:
2023
Tipo del documento:
Article
País de afiliación:
India