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- W2965156742 abstract "Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with diverse drivers of disease progression and mechanisms of therapeutic resistance. We conducted deep phenotypic characterization of CRPC metastases and patient-derived xenograft (PDX) lines using whole genome RNA sequencing, gene set enrichment analysis and immunohistochemistry. Our analyses revealed five mCRPC phenotypes based on the expression of well-characterized androgen receptor (AR) or neuroendocrine (NE) genes: (i) AR-high tumors (ARPC), (ii) AR-low tumors (ARLPC), (iii) amphicrine tumors composed of cells co-expressing AR and NE genes (AMPC), (iv) double-negative tumors (i.e. AR-/NE-; DNPC) and (v) tumors with small cell or NE gene expression without AR activity (SCNPC). RE1-silencing transcription factor (REST) activity, which suppresses NE gene expression, was lost in AMPC and SCNPC PDX models. However, knockdown of REST in cell lines revealed that attenuated REST activity drives the AMPC phenotype but is not sufficient for SCNPC conversion. We also identified a subtype of DNPC tumors with squamous differentiation and generated an encompassing 26-gene transcriptional signature that distinguished the five mCRPC phenotypes. Together, our data highlight the central role of AR and REST in classifying treatment-resistant mCRPC phenotypes. These molecular classifications could potentially guide future therapeutic studies and clinical trial design." @default.
- W2965156742 created "2019-08-13" @default.
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- W2965156742 date "2019-09-16" @default.
- W2965156742 modified "2023-10-13" @default.
- W2965156742 title "Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer" @default.
- W2965156742 cites W146177628 @default.
- W2965156742 cites W1505821987 @default.
- W2965156742 cites W1949146490 @default.
- W2965156742 cites W1966517158 @default.
- W2965156742 cites W1980256159 @default.
- W2965156742 cites W1985143543 @default.
- W2965156742 cites W1986151600 @default.
- W2965156742 cites W1989427739 @default.
- W2965156742 cites W1997254455 @default.
- W2965156742 cites W1999139669 @default.
- W2965156742 cites W2000056288 @default.
- W2965156742 cites W2001158829 @default.
- W2965156742 cites W2001994418 @default.
- W2965156742 cites W2014067589 @default.
- W2965156742 cites W2025290884 @default.
- W2965156742 cites W2026507797 @default.
- W2965156742 cites W2027075319 @default.
- W2965156742 cites W2036048598 @default.
- W2965156742 cites W2038963685 @default.
- W2965156742 cites W2039511031 @default.
- W2965156742 cites W2042356721 @default.
- W2965156742 cites W2061716134 @default.
- W2965156742 cites W2061932727 @default.
- W2965156742 cites W2064293531 @default.
- W2965156742 cites W2067892063 @default.
- W2965156742 cites W2078444870 @default.
- W2965156742 cites W2090945178 @default.
- W2965156742 cites W2091574906 @default.
- W2965156742 cites W2093876854 @default.
- W2965156742 cites W2093932877 @default.
- W2965156742 cites W2097121410 @default.
- W2965156742 cites W2100575592 @default.
- W2965156742 cites W2106315111 @default.
- W2965156742 cites W2110574342 @default.
- W2965156742 cites W2114104545 @default.
- W2965156742 cites W2119504728 @default.
- W2965156742 cites W2131478115 @default.
- W2965156742 cites W2136452881 @default.
- W2965156742 cites W2137467802 @default.
- W2965156742 cites W2137974207 @default.
- W2965156742 cites W2139773658 @default.
- W2965156742 cites W2140568660 @default.
- W2965156742 cites W2140729960 @default.
- W2965156742 cites W2148643283 @default.
- W2965156742 cites W2155062006 @default.
- W2965156742 cites W2159707944 @default.
- W2965156742 cites W2160450758 @default.
- W2965156742 cites W2190954851 @default.
- W2965156742 cites W2262087934 @default.
- W2965156742 cites W2288055189 @default.
- W2965156742 cites W2292362441 @default.
- W2965156742 cites W2303686061 @default.
- W2965156742 cites W2356434884 @default.
- W2965156742 cites W2408089991 @default.
- W2965156742 cites W2540786849 @default.
- W2965156742 cites W2554787935 @default.
- W2965156742 cites W2565408884 @default.
- W2965156742 cites W2567986926 @default.
- W2965156742 cites W2571250257 @default.
- W2965156742 cites W2583236130 @default.
- W2965156742 cites W2594904943 @default.
- W2965156742 cites W2607041430 @default.
- W2965156742 cites W2610194775 @default.
- W2965156742 cites W2762381618 @default.
- W2965156742 cites W2768353180 @default.
- W2965156742 cites W2800224432 @default.
- W2965156742 cites W2801671624 @default.
- W2965156742 cites W2841858285 @default.
- W2965156742 cites W2886821920 @default.
- W2965156742 cites W2894741998 @default.
- W2965156742 cites W2895496651 @default.