Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer.
Cancer Res
; 82(2): 221-234, 2022 01 15.
Article
in En
| MEDLINE
| ID: mdl-34625422
ABSTRACT
The retinoblastoma tumor suppressor (RB) is a critical regulator of E2F-dependent transcription, controlling a multitude of protumorigenic networks including but not limited to cell-cycle control. Here, genome-wide assessment of E2F1 function after RB loss in isogenic models of prostate cancer revealed unexpected repositioning and cooperation with oncogenic transcription factors, including the major driver of disease progression, the androgen receptor (AR). Further investigation revealed that observed AR/E2F1 cooperation elicited novel transcriptional networks that promote cancer phenotypes, especially as related to evasion of cell death. These observations were reflected in assessment of human disease, indicating the clinical relevance of the AR/E2F1 cooperome in prostate cancer. Together, these studies reveal new mechanisms by which RB loss induces cancer progression and highlight the importance of understanding the targets of E2F1 function. SIGNIFICANCE:
This study identifies that RB loss in prostate cancer drives cooperation between AR and E2F1 as coregulators of transcription, which is linked to the progression of advanced disease.
Full text:
1
Collection:
01-internacional
Health context:
6_ODS3_enfermedades_notrasmisibles
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
/
Signal Transduction
/
Receptors, Androgen
/
Oncogene Proteins
/
Ubiquitin-Protein Ligases
/
E2F1 Transcription Factor
/
Retinoblastoma Binding Proteins
/
Carcinogenesis
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
/
Male
Language:
En
Journal:
Cancer Res
Year:
2022
Document type:
Article