Cyrta, JoannaJoannaCyrtaAugspach, Anke KatharinaAnke KatharinaAugspachDe Filippo, Maria RosariaMaria RosariaDe FilippoPrandi, DavideDavidePrandiThienger, Phillip DominikPhillip DominikThiengerBenelli, MatteoMatteoBenelliCooley, VictoriaVictoriaCooleyBareja, RohanRohanBarejaWilkes, DavidDavidWilkesChae, Sung-SukSung-SukChaeCavaliere, PaolaPaolaCavaliereDephoure, NoahNoahDephoureUldry, Anne-ChristineAnne-ChristineUldryBraga, Sophie Marie-PierreSophie Marie-PierreBragaRoma, LucaLucaRomaCohen, SandraSandraCohenJaquet, MurielMurielJaquetBrandt, Laura PatriciaLaura PatriciaBrandtAlshalalfa, MohammedMohammedAlshalalfaPuca, LoredanaLoredanaPucaSboner, AndreaAndreaSbonerFeng, FelixFelixFengWang, ShangqianShangqianWangBeltran, HimishaHimishaBeltranLotan, TamaraTamaraLotanSpahn, MartinMartinSpahnKruithof-de Julio, MariannaMariannaKruithof-de JulioChen, YuYuChenBallman, Karla VKarla VBallmanDemichelis, FrancescaFrancescaDemichelisPiscuoglio, SalvatoreSalvatorePiscuoglioRubin, Mark AndrewMark AndrewRubin2024-09-202024-09-202020-11-03https://boris-portal.unibe.ch/handle/20.500.12422/45113Advanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in around 10-20% of these patients is lineage plasticity, which manifests in a partial or complete small cell or neuroendocrine prostate cancer (NEPC) phenotype. Here, we investigate the role of the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex in NEPC. Using large patient datasets, patient-derived organoids and cancer cell lines, we identify mSWI/SNF subunits that are deregulated in NEPC and demonstrate that SMARCA4 (BRG1) overexpression is associated with aggressive disease. We also show that SWI/SNF complexes interact with different lineage-specific factors in NEPC compared to prostate adenocarcinoma. These data point to a role for mSWI/SNF complexes in therapy-related lineage plasticity, which may also be relevant for other solid tumors.en600 - Technology::610 - Medicine & healtharticle10.7892/boris.1480553314457610.1038/s41467-020-19328-1