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• W2893677139 abstract "Abstract The incidence of aggressive neuroendocrine prostate cancers (NEPC) related to androgen-deprivation therapy (ADT) is rising. NEPC is still poorly understood, such as its neuroendocrine differentiation (NED) and angiogenic phenotypes. Here we reveal that NED and angiogenesis are molecularly connected through EZH2 (enhancer of zeste homolog 2). NED and angiogenesis are both regulated by ADT-activated CREB (cAMP response element-binding protein) that in turn enhances EZH2 activity. We also uncover anti-angiogenic factor TSP1 (thrombospondin-1, THBS1) as a direct target of EZH2 epigenetic repression. TSP1 is downregulated in advanced prostate cancer patient samples and negatively correlates with NE markers and EZH2. Furthermore, castration activates the CREB/EZH2 axis, concordantly affecting TSP1, angiogenesis and NE phenotypes in tumor xenografts. Notably, repressing CREB inhibits the CREB/EZH2 axis, tumor growth, NED, and angiogenesis in vivo. Taken together, we elucidate a new critical pathway, consisting of CREB/EZH2/TSP1, underlying ADT-enhanced NED and angiogenesis during prostate cancer progression." @default.
• W2893677139 created "2018-10-05" @default.
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• W2893677139 date "2018-10-04" @default.
• W2893677139 modified "2023-10-14" @default.
• W2893677139 title "Androgen deprivation promotes neuroendocrine differentiation and angiogenesis through CREB-EZH2-TSP1 pathway in prostate cancers" @default.
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• W2893677139 doi "https://doi.org/10.1038/s41467-018-06177-2" @default.
• W2893677139 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6172226" @default.
• W2893677139 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30287808" @default.
• W2893677139 hasPublicationYear "2018" @default.
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