FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3186914507> ?p ?o ?g. }

• W3186914507 endingPage "5490" @default.
• W3186914507 startingPage "5477" @default.
• W3186914507 abstract "Abstract Castration-resistant prostate cancer (CRPC) is a lethal stage of disease in which androgen receptor (AR) signaling is persistent despite androgen deprivation therapy (ADT). Most studies have focused on investigating cell-autonomous alterations in CRPC, while the contributions of the tumor microenvironment are less well understood. Here we sought to determine the role of tumor-associated macrophages in CRPC, based upon their role in cancer progression and therapeutic resistance. In a syngeneic model that reflected the mutational landscape of CRPC, macrophage depletion resulted in a reduced transcriptional signature for steroid and bile acid synthesis, indicating potential perturbation of cholesterol metabolism. As cholesterol is the precursor of the five major types of steroid hormones, we hypothesized that macrophages were regulating androgen biosynthesis within the prostate tumor microenvironment. Macrophage depletion reduced androgen levels within prostate tumors and restricted AR nuclear localization in vitro and in vivo. Macrophages were also cholesterol-rich and were able to transfer cholesterol to tumor cells in vitro. AR nuclear translocation was inhibited by activation of liver X receptor (LXR)-β, the master regulator of cholesterol homeostasis. Consistent with these data, macrophage depletion extended survival during ADT and the presence of macrophages correlated with therapeutic resistance in patient-derived explants. Taken together, these findings support the therapeutic targeting of macrophages in CRPC. Significance: These results suggest that macrophage-targeted therapies can be combined with androgen deprivation therapy to treat patients with prostate cancer by limiting cholesterol bioavailability and the production of intratumoral androgens. See related commentary by Al-Janabi and Lewis, p. 5399" @default.
• W3186914507 created "2021-08-02" @default.
• W3186914507 creator A5002876951 @default.
• W3186914507 creator A5009931242 @default.
• W3186914507 creator A5015862974 @default.
• W3186914507 creator A5017353282 @default.
• W3186914507 creator A5021009961 @default.
• W3186914507 creator A5032533490 @default.
• W3186914507 creator A5034308538 @default.
• W3186914507 creator A5057043456 @default.
• W3186914507 creator A5058322240 @default.
• W3186914507 creator A5059851198 @default.
• W3186914507 creator A5060238737 @default.
• W3186914507 creator A5060579879 @default.
• W3186914507 creator A5067008882 @default.
• W3186914507 creator A5078872209 @default.
• W3186914507 creator A5082346230 @default.
• W3186914507 creator A5086999753 @default.
• W3186914507 date "2021-07-23" @default.
• W3186914507 modified "2023-10-17" @default.
• W3186914507 title "Macrophage-Derived Cholesterol Contributes to Therapeutic Resistance in Prostate Cancer" @default.
• W3186914507 cites W116258950 @default.
• W3186914507 cites W1541739901 @default.
• W3186914507 cites W1543678657 @default.
• W3186914507 cites W1749239599 @default.
• W3186914507 cites W1968545383 @default.
• W3186914507 cites W1969438318 @default.
• W3186914507 cites W1973165542 @default.
• W3186914507 cites W1973745498 @default.
• W3186914507 cites W1986799557 @default.
• W3186914507 cites W1999378743 @default.
• W3186914507 cites W2006001375 @default.
• W3186914507 cites W2009171847 @default.
• W3186914507 cites W2026878412 @default.
• W3186914507 cites W2051030011 @default.
• W3186914507 cites W2052964297 @default.
• W3186914507 cites W2062135418 @default.
• W3186914507 cites W2074990743 @default.
• W3186914507 cites W2075137329 @default.
• W3186914507 cites W2088516053 @default.
• W3186914507 cites W2105949723 @default.
• W3186914507 cites W2115736737 @default.
• W3186914507 cites W2116581148 @default.
• W3186914507 cites W2118180586 @default.
• W3186914507 cites W2121158863 @default.
• W3186914507 cites W2125200489 @default.
• W3186914507 cites W2136722399 @default.
• W3186914507 cites W2139677318 @default.
• W3186914507 cites W2142530756 @default.
• W3186914507 cites W2142924577 @default.
• W3186914507 cites W2147166694 @default.
• W3186914507 cites W2159810380 @default.
• W3186914507 cites W2161112598 @default.
• W3186914507 cites W2165155335 @default.
• W3186914507 cites W2170561747 @default.
• W3186914507 cites W2173477069 @default.
• W3186914507 cites W2317623391 @default.
• W3186914507 cites W2345296224 @default.
• W3186914507 cites W2727380696 @default.
• W3186914507 cites W2749550628 @default.
• W3186914507 cites W2769504061 @default.
• W3186914507 cites W2783471328 @default.
• W3186914507 cites W2790054724 @default.
• W3186914507 cites W2804058066 @default.
• W3186914507 cites W2804540798 @default.
• W3186914507 cites W2807581044 @default.
• W3186914507 cites W2811252608 @default.
• W3186914507 cites W2888064785 @default.
• W3186914507 cites W2904355372 @default.
• W3186914507 cites W2913214687 @default.
• W3186914507 cites W2914311347 @default.
• W3186914507 cites W2934055254 @default.
• W3186914507 cites W2947358336 @default.
• W3186914507 cites W2967990981 @default.
• W3186914507 cites W3021273165 @default.
• W3186914507 cites W3023444635 @default.
• W3186914507 cites W3042849878 @default.
• W3186914507 cites W3085213187 @default.
• W3186914507 cites W3092635944 @default.
• W3186914507 cites W3111900913 @default.
• W3186914507 cites W4322700960 @default.
• W3186914507 doi "https://doi.org/10.1158/0008-5472.can-20-4028" @default.
• W3186914507 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8563406" @default.
• W3186914507 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34301759" @default.
• W3186914507 hasPublicationYear "2021" @default.
• W3186914507 type Work @default.
• W3186914507 sameAs 3186914507 @default.
• W3186914507 citedByCount "33" @default.
• W3186914507 countsByYear W31869145072021 @default.
• W3186914507 countsByYear W31869145072022 @default.
• W3186914507 countsByYear W31869145072023 @default.
• W3186914507 crossrefType "journal-article" @default.
• W3186914507 hasAuthorship W3186914507A5002876951 @default.
• W3186914507 hasAuthorship W3186914507A5009931242 @default.
• W3186914507 hasAuthorship W3186914507A5015862974 @default.
• W3186914507 hasAuthorship W3186914507A5017353282 @default.
• W3186914507 hasAuthorship W3186914507A5021009961 @default.
• W3186914507 hasAuthorship W3186914507A5032533490 @default.

• next