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Blomme, Arnaud; Ford, Catriona A; Mui, Ernest; Patel, Rachana; Ntala, Chara; Jamieson, Lauren E; Planque, Mélanie; McGregor, Grace H; Peixoto, Paul; Hervouet, Eric; Nixon, Colin; Salji, Mark; Gaughan, Luke; Markert, Elke; Repiscak, Peter; Sumpton, David; Blanco, Giovanny Rodriguez; Lilla, Sergio; Kamphorst, Jurre J; Graham, Duncan; Faulds, Karen; MacKay, Gillian M; Fendt, Sarah-Maria; Zanivan, Sara; Leung, Hing Y
Nature communications, 05/2020, Letnik: 11, Številka: 1Journal Article, Web Resource
Despite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation of AR signalling remains the main driver of castration-resistant prostate cancer (CRPC) progression. In this study, we perform a comprehensive unbiased characterisation of LNCaP cells chronically exposed to multiple AR inhibitors (ARI). Combined proteomics and metabolomics analyses implicate an acquired metabolic phenotype common in ARI-resistant cells and associated with perturbed glucose and lipid metabolism. To exploit this phenotype, we delineate a subset of proteins consistently associated with ARI resistance and highlight mitochondrial 2,4-dienoyl-CoA reductase (DECR1), an auxiliary enzyme of beta-oxidation, as a clinically relevant biomarker for CRPC. Mechanistically, DECR1 participates in redox homeostasis by controlling the balance between saturated and unsaturated phospholipids. DECR1 knockout induces ER stress and sensitises CRPC cells to ferroptosis. In vivo, DECR1 deletion impairs lipid metabolism and reduces CRPC tumour growth, emphasizing the importance of DECR1 in the development of treatment resistance.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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