Abstract
The dysregulation of ETS family transcription factors drives human prostate cancer. The majority of prostate cancer is the result of chromosomal rearrangements that lead to aberrant ETS gene expression. The mechanisms that lead to fusion independent ETS factor upregulation and prostate oncogenesis remain 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 occurs 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.
Competing Interest Statement
The authors have declared no competing interest.
