PRAME induces genomic instability in uveal melanoma.

Autor: Kurtenbach S; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Sanchez MI; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Kuznetsoff J; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Rodriguez DA; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Weich N; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA., Dollar JJ; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Cruz A; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Kurtenbach S; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Field MG; Minnesota Eye Consultants, Bloomington, MN, USA., Durante MA; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Decatur C; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Sorouri M; Department of Ophthalmology and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA., Lai F; School of Life Sciences, Yunnan University, Kunming, China., Yenisehirli G; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Fang B; Proteomics and Metabolomics Core, The Moffitt Cancer Center and Research Institute, Tampa, FL, USA., Shiekhattar R; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA., Pelaez D; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Correa ZM; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Verdun RE; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA., Harbour JW; Department of Ophthalmology and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. William.Harbour@utsouthwestern.edu.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2024 Feb; Vol. 43 (8), pp. 555-565. Date of Electronic Publication: 2023 Nov 29.
DOI: 10.1038/s41388-023-02887-0
Abstrakt: PRAME is a CUL2 ubiquitin ligase subunit that is normally expressed in the testis but becomes aberrantly overexpressed in many cancer types in association with aneuploidy and metastasis. Here, we show that PRAME is expressed predominantly in spermatogonia around the time of meiotic crossing-over in coordination with genes mediating DNA double strand break repair. Expression of PRAME in somatic cells upregulates pathways involved in meiosis, chromosome segregation and DNA repair, and it leads to increased DNA double strand breaks, telomere dysfunction and aneuploidy in neoplastic and non-neoplastic cells. This effect is mediated at least in part by ubiquitination of SMC1A and altered cohesin function. PRAME expression renders cells susceptible to inhibition of PARP1/2, suggesting increased dependence on alternative base excision repair pathways. These findings reveal a distinct oncogenic function of PRAME that can be targeted therapeutically in cancer.
(© 2023. The Author(s).)
Databáze: MEDLINE
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