Cancer stem cells (CSCs) are considered one of the key contributors to chemoresistance and tumor recurrence. Therefore, the precise identification of reliable CSC markers and clarification of the intracellular signaling involved in CSCs remains a great challenge in fields relating to cancer biology. Here, we implemented a novel chemoresistant prostate cancer patient-derived xenograft (PDX) model in NOD/SCID mice and identified CD54 as a candidate gene among the most highly enriched gene expression profiles in prostate tumors exposed to chronic cisplatin administration. Additional in vitro and in vivo assays showed that CD54 played a critical role in the self-renewal and tumorigenesis of prostate CSCs. Moreover, silencing CD54 greatly reduced the tumorigenesis of prostate cancers both in vitro and in vivo and significantly extended the survival time of tumor-bearing mice in a prostate cancer xenograft model. Dissection of the molecular mechanism revealed that the p38-Notch1 axis was the main downstream signaling pathway in CD54-mediated regulation of CSCs in prostate cancers. Together, these results established that CD54 could be a novel reliable prostate CSC marker and provided a new potential therapeutic target in prostate cancer via CD54-Notch1 signaling.

中文翻译：

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CD54-NOTCH1轴控制人类前列腺癌中的肿瘤起始和癌症干细胞功能。

癌症干细胞（CSC）被认为是化学抗药性和肿瘤复发的关键因素之一。因此，在与癌症生物学有关的领域中，可靠的CSC标记物的精确鉴定和CSC所涉及的细胞内信号的澄清仍然是一个巨大的挑战。在这里，我们在NOD / SCID小鼠中实施了一种新型的化学抗性来自前列腺癌患者的异种移植（PDX）模型，并将CD54鉴定为暴露于慢性顺铂给药的前列腺肿瘤中最富集的基因表达谱中的候选基因。其他体外和体内试验表明，CD54在前列腺CSC的自我更新和肿瘤发生中起关键作用。而且，沉默的CD54大大降低了体内和体外前列腺癌的肿瘤发生，并显着延长了荷瘤小鼠在前列腺癌异种移植模型中的存活时间。分子机制的解剖揭示，p38-Notch1轴是CD54介导的前列腺癌CSCs调控的主要下游信号通路。总之，这些结果确定了CD54可能是一种新颖可靠的前列腺CSC标记物，并通过CD54-Notch1信号传导为前列腺癌提供了新的潜在治疗靶标。