前列腺癌
翻译(生物学)
雄激素受体
癌症研究
医学
癌症
内科学
生物
信使核糖核酸
生物化学
基因
作者
Cheng Zou,Wenchao Li,Yuanzhen Zhang,Ninghan Feng,Saisai Chen,Lianlian Yan,Qinju He,Kai Wang,Wenjun Li,Yingying Li,Yang Wang,Bin Xu,Dingxiao Zhang
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2024-04-03
卷期号:10 (14)
被引量:5
标识
DOI:10.1126/sciadv.adm7098
摘要
Histopathological heterogeneity is a hallmark of prostate cancer (PCa). Using spatial and parallel single-nucleus transcriptomics, we report an androgen receptor (AR)-positive but neuroendocrine-null primary PCa subtype with morphologic and molecular characteristics of small cell carcinoma. Such small cell-like PCa (SCLPC) is clinically aggressive with low AR, but high stemness and proliferation, activity. Molecular characterization prioritizes protein translation, represented by up-regulation of many ribosomal protein genes, and SP1, a transcriptional factor that drives SCLPC phenotype and overexpresses in castration-resistant PCa (CRPC), as two potential therapeutic targets in AR-indifferent CRPC. An SP1-specific inhibitor, plicamycin, effectively suppresses CRPC growth in vivo. Homoharringtonine, a Food And Drug Administration-approved translation elongation inhibitor, impedes CRPC progression in preclinical models and patients with CRPC. We construct an SCLPC-specific signature capable of stratifying patients for drug selectivity. Our studies reveal the existence of SCLPC in admixed PCa pathology, which may mediate tumor relapse, and establish SP1 and translation elongation as actionable therapeutic targets for CRPC.
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