Autor: |
Nehal Gupta, Hanbing Song, Wei Wu, Rovingaile K Ponce, Yone K Lin, Ji Won Kim, Eric J Small, Felix Y Feng, Franklin W Huang, Ross A Okimoto |
Jazyk: |
angličtina |
Rok vydání: |
2022 |
Předmět: |
|
Zdroj: |
eLife, Vol 11 (2022) |
Druh dokumentu: |
article |
ISSN: |
2050-084X |
DOI: |
10.7554/eLife.77072 |
Popis: |
Human prostate cancer can result from chromosomal rearrangements that lead to aberrant ETS gene expression. The mechanisms that lead to fusion-independent ETS factor upregulation and prostate oncogenesis remain relatively unknown. Here, we show that two neighboring transcription factors, Capicua (CIC) and ETS2 repressor factor (ERF), which are co-deleted in human prostate tumors can drive prostate oncogenesis. Concurrent CIC and ERF loss commonly occur through focal genomic deletions at chromosome 19q13.2. Mechanistically, CIC and ERF co-bind the proximal regulatory element and mutually repress the ETS transcription factor, ETV1. Targeting ETV1 in CIC and ERF-deficient prostate cancer limits tumor growth. Thus, we have uncovered a fusion-independent mode of ETS transcriptional activation defined by concurrent loss of CIC and ERF. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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