RT Journal Article
T1 CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel driver of metastasis in prostate cancer
A1 Rodrigo-Faus, María
A1 Vincelle-Nieto, Africa
A1 Vidal, Natalia
A1 Puente Vázquez, Javier
A1 Saiz-Pardo Sanz, Melchor
A1 López-García, Alejandra
A1 Mendiburu-Eliçabe Garganta, Marina
A1 Palao, Nerea
A1 Baquero, Cristina
A1 Cuesta Martínez, Ángel
A1 Qu, Hui-Qi
A1 Hakonarson, Hakon
A1 Musteanu, Mónica
A1 Reyes-Palomares, Armando
A1 Porras Gallo, María Almudena
A1 Bragado, Paloma
A1 Gutierrez-Uzquiza, Alvaro
A1 Reyes Palomares, Armando Adolfo
A1 Bragado Domingo, Paloma
A1 Gutiérrez Uzquiza, Álvaro
AB Due to the limited effectiveness of current treatments, the survival rate of patients with metastatic castrationresistant prostate cancer (mCRPC) is significantly reduced. Consequently, it is imperative to identify novel therapeutic targets for managing these patients. Since the invasive ability of cells is crucial for establishing and maintaining metastasis, the aim of this study was to identify the essential regulators of invasive abilities ofmCRPC cells by conducting two independent high-throughput CRISPR/Cas9 screenings. Furthermore, some of the top hits were validated using siRNA technology, with protein arginine methyltransferase 7 (PRMT7) emerging as the most promising candidate. We demonstrated that its inhibition or depletion via genetic or pharmacological approaches significantly reduces invasive, migratory and proliferative abilities of mCRPC cells in vitro. Moreover, we confirmed that PRMT7 ablation reduces cell dissemination in chicken chorioallantoic membrane and mouse xenograft assays. Molecularly, PRMT7 reprograms the expression of several adhesion molecules by methylating various transcription factors, such as FoxK1, resulting in the loss of adhesion from the primary tumor and increased motility of mCRPC cells. Furthermore, PRMT7 higher expression correlates with tumor aggressivity and poor overall survival in prostate cancer patients. Thus, this study demonstrates that PRMT7 is a potential therapeutic target and potential biomarker for mPCa
PB Elsevier
YR 2023
FD 2023-07-22
LK https://hdl.handle.net/20.500.14352/113457
UL https://hdl.handle.net/20.500.14352/113457
LA eng
NO Comunidad de Madrid
NO Regional Programme of Research and Technological Innovation for Young Doctors
DS Docta Complutense
RD 18 abr 2025