Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence.
Nucleic Acids Res
; 44(9): 4105-22, 2016 05 19.
Article
en En
| MEDLINE
| ID: mdl-26743006
ABSTRACT
Identifying prostate cancer-driving transcription factors (TFs) in addition to the androgen receptor promises to improve our ability to effectively diagnose and treat this disease. We employed an integrative genomics analysis of master TFs CREB1 and FoxA1 in androgen-dependent prostate cancer (ADPC) and castration-resistant prostate cancer (CRPC) cell lines, primary prostate cancer tissues and circulating tumor cells (CTCs) to investigate their role in defining prostate cancer gene expression profiles. Combining genome-wide binding site and gene expression profiles we define CREB1 as a critical driver of pro-survival, cell cycle and metabolic transcription programs. We show that CREB1 and FoxA1 co-localize and mutually influence each other's binding to define disease-driving transcription profiles associated with advanced prostate cancer. Gene expression analysis in human prostate cancer samples found that CREB1/FoxA1 target gene panels predict prostate cancer recurrence. Finally, we showed that this signaling pathway is sensitive to compounds that inhibit the transcription co-regulatory factor MED1. These findings not only reveal a novel, global transcriptional co-regulatory function of CREB1 and FoxA1, but also suggest CREB1/FoxA1 signaling is a targetable driver of prostate cancer progression and serves as a biomarker of poor clinical outcomes.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Proteína de Unión a Elemento de Respuesta al AMP Cíclico
/
Factor Nuclear 3-alfa del Hepatocito
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Recurrencia Local de Neoplasia
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Aged
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Aged80
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos