{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Baratchian M"],"funding":["HHS | National Institutes of Health","HHS | National Institutes of Health (NIH)","HHS | NIH | National Cancer Institute","NIAID NIH HHS","Medical Research Council","U.S. Department of Defense","NCI NIH HHS","HHS | NIH | National Institute of Allergy and Infectious Diseases","HHS | NIH | National Cancer Institute (NCI)","HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)"],"pagination":["e2114324119"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9173765"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["119(21)"],"pubmed_abstract":["Antiandrogen strategies remain the prostate cancer treatment backbone, but drug resistance develops. We show that androgen blockade in prostate cancer leads to derepression of retroelements (REs) followed by a double-stranded RNA (dsRNA)-stimulated interferon response that blocks tumor growth. A forward genetic approach identified H3K9 trimethylation (H3K9me3) as an essential epigenetic adaptation to antiandrogens, which enabled transcriptional silencing of REs that otherwise stimulate interferon signaling and glucocorticoid receptor expression. Elevated expression of terminal H3K9me3 writers was associated with poor patient hormonal therapy outcomes. Forced expression of H3K9me3 writers conferred resistance, whereas inhibiting H3K9-trimethylation writers and readers restored RE expression"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["H3K9 methylation drives resistance to androgen receptor-antagonist therapy in prostate cancer."],"pmcid":["PMC9173765"],"funding_grant_id":["R50CA251961","2P01CA062220","R01AI13592","R01CA236780","R01 AI135922","T32 CA094186","1S10OD019972-01","R01 CA261995","R01 CA249279","W81XWH-20-1-0137","R01CA172382"],"pubmed_authors":["Stark GR","Li J","Tiwari R","Makarov V","Varadan V","Chakraborty AA","Baratchian M","Berk M","Chakravarthy A","Sharifi N","Khalighi S","Guerinot A","Chan TA","Silverman RH","De Carvalho DD","Yuan W","de Bono J"],"additional_accession":[]},"is_claimable":false,"name":"H3K9 methylation drives resistance to androgen receptor-antagonist therapy in prostate cancer.","description":"Antiandrogen strategies remain the prostate cancer treatment backbone, but drug resistance develops. We show that androgen blockade in prostate cancer leads to derepression of retroelements (REs) followed by a double-stranded RNA (dsRNA)-stimulated interferon response that blocks tumor growth. A forward genetic approach identified H3K9 trimethylation (H3K9me3) as an essential epigenetic adaptation to antiandrogens, which enabled transcriptional silencing of REs that otherwise stimulate interferon signaling and glucocorticoid receptor expression. Elevated expression of terminal H3K9me3 writers was associated with poor patient hormonal therapy outcomes. Forced expression of H3K9me3 writers conferred resistance, whereas inhibiting H3K9-trimethylation writers and readers restored RE expression","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2025-04-03T22:37:40.694Z","creation":"2025-04-03T22:37:40.694Z"},"accession":"S-EPMC9173765","cross_references":{"pubmed":["35584120"],"doi":["10.1073/pnas.2114324119"]}}