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- W4361946319 abstract "<div>Abstract<p><b>Purpose:</b> To elucidate the role and molecular mechanism of Numb in prostate cancer and the functional contribution of Numb<sup>−/low</sup> prostate cancer cells in castration resistance.</p><p><b>Experimental Design:</b> The expression of Numb was assessed using multiple <i>Oncomine</i> datasets and prostate cancer tissues from both humans and mice. The biological effects of the overexpression and knockdown of Numb in human prostate cancer cell lines were investigated <i>in vitro</i> and <i>in vivo</i>. In addition, we developed a reliable approach to distinguish between prostate cancer cell populations with a high or low endogenous expression of Numb protein using a Numb promoter–based lentiviral reporter system. The difference between Numb<sup>−/low</sup> and Numb<sup>high</sup> prostate cancer cells in the response to androgen-deprivation therapy (ADT) was then tested. The likely downstream factors of Numb were analyzed using luciferase reporter assays, immunoblotting, and quantitative real-time PCR.</p><p><b>Results:</b> We show here that Numb was downregulated and negatively correlated with prostate cancer advancement. Functionally, Numb played an inhibitory role in xenograft prostate tumor growth and castration-resistant prostate cancer development by suppressing Notch and Hedgehog signaling. Using a <i>Numb</i> promoter–based lentiviral reporter system, we were able to distinguish Numb<sup>−/low</sup> prostate cancer cells from Numb<sup>high</sup> cells. Numb<sup>−/low</sup> prostate cancer cells were smaller and quiescent, preferentially expressed Notch and Hedgehog downstream and stem-cell–associated genes, and associated with a greater resistance to ADT. The inhibition of the Notch and Hedgehog signaling pathways significantly increased apoptosis in Numb<sup>−/low</sup> cells in response to ADT.</p><p><b>Conclusions:</b> Numb<sup>−/low</sup> enriches a castration-resistant prostate cancer cell subpopulation that is associated with unregulated Notch and Hedgehog signaling. <i>Clin Cancer Res; 23(21); 6744–56. ©2017 AACR</i>.</p></div>" @default.
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- W4361946319 date "2023-03-31" @default.
- W4361946319 modified "2023-10-18" @default.
- W4361946319 title "Data from Numb<sup>−/low</sup> Enriches a Castration-Resistant Prostate Cancer Cell Subpopulation Associated with Enhanced Notch and Hedgehog Signaling" @default.
- W4361946319 doi "https://doi.org/10.1158/1078-0432.c.6527117" @default.
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