Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer

Amy C. Mandigo, Ayesha A. Shafi, Jennifer J. McCann, Wei Yuan, Talya S. Laufer, Denisa Bogdan, Lewis Gallagher, Emanuela Dylgjeri, Galina Semenova, Irina A. Vasilevskaya, Matthew J. Schiewer, Chris M. McNair, Johann S. de Bono, Karen E. Knudsen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish
Pages (from-to)221-234
Number of pages14
JournalCancer Research
Volume82
Issue number2
DOIs
StatePublished - 15 Jan 2022
Externally publishedYes

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