The CIC-ERF co-deletion underlies fusion-independent activation of ETS family member, ETV1, to drive prostate cancer progression

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.
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