Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer.
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ICR Authors
Authors
Mandigo, AC
Shafi, AA
McCann, JJ
Yuan, W
Laufer, TS
Bogdan, D
Gallagher, L
Dylgjeri, E
Semenova, G
Vasilevskaya, IA
Schiewer, MJ
McNair, CM
de Bono, JS
Knudsen, KE
Shafi, AA
McCann, JJ
Yuan, W
Laufer, TS
Bogdan, D
Gallagher, L
Dylgjeri, E
Semenova, G
Vasilevskaya, IA
Schiewer, MJ
McNair, CM
de Bono, JS
Knudsen, KE
Document Type
Journal Article
Date
2022-01-15
Date Accepted
2021-09-09
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.
Citation
Cancer Research, 2022, 82 (2), pp. 221 - 234
Source Title
Cancer Research
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
0008-5472
eISSN
1538-7445
Collections
Research Team
Cancer Biomarkers
PrCa Targeted Therapy
PrCa Targeted Therapy