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

Autor:	Gupta N; Department of Medicine, University of California, San Francisco, United States., Song H; Department of Medicine, University of California, San Francisco, United States., Wu W; Department of Medicine, University of California, San Francisco, United States., Ponce RK; Department of Medicine, University of California, San Francisco, United States., Lin YK; Department of Medicine, University of California, San Francisco, United States., Kim JW; Department of Medicine, University of California, San Francisco, United States., Small EJ; Department of Medicine, University of California, San Francisco, United States.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, United States., Feng FY; Department of Medicine, University of California, San Francisco, United States.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, United States.; Department of Radiation Oncology, University of California, San Francisco, United States., Huang FW; Department of Medicine, University of California, San Francisco, United States.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, United States., Okimoto RA; Department of Medicine, University of California, San Francisco, United States.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 Nov 16; Vol. 11. Date of Electronic Publication: 2022 Nov 16.
DOI:	10.7554/eLife.77072
Abstrakt:	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 . Competing Interests: NG, HS, WW, RP, YL, JK, ES, FF, FH, RO No competing interests declared (© 2022, Gupta et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu