Prostate cancer as a dedifferentiated organ: androgen receptor, cancer stem cells, and cancer stemness.
Prostate cancer as a dedifferentiated organ: androgen receptor, cancer stem cells, and cancer stemness.
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DOI：
10.1042/ebc20220003
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发表时间：
2022-09-16
影响因子：
6.4
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中科院分区：
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癌症进展的特征在于并由分化表型的逐渐丧失和干细胞样特征的获得驱动。在前列腺癌（PCa）中，雄激素受体（AR）信号传导对癌症生长、进展和治疗耐药性的出现很重要。几十年来，靶向AR信号传导轴一直是PCa治疗的支柱。然而，相对于低级别PCa，高级别癌症中转录水平的AR信号传导减少，AR表达的丧失促进干细胞样表型，这表明对AR靶向治疗的抗性的出现可能与AR信号传导的丧失和干性的获得相关。在目前的小型审查，我们首先讨论PCa的角度来看，一个异常的器官越来越失调分化，并讨论在PCa的进展过程中AR信号的作用。然后，我们专注于前列腺癌干细胞（PCSC）和AR信号之间的关系。我们进一步阐述了目前使用基于转录组的干性富集特征来评估泛癌症数据集中致癌去分化（癌症干性）程度的方法，并提出了在PCa发展谱中对基于转录组的干性进行评分的临床意义。我们的讨论强调了评估PCa谱中干细胞样特征（干性评分）和AR信号传导活性的动态变化的重要性。
Cancer progression is characterized and driven by gradual loss of a differentiated phenotype and gain of stem cell-like features. In prostate cancer (PCa), androgen receptor (AR) signaling is important for cancer growth, progression, and emergence of therapy resistance. Targeting the AR signaling axis has been, over the decades, the mainstay of PCa therapy. However, AR signaling at the transcription level is reduced in high-grade cancer relative to low-grade PCa and loss of AR expression promotes a stem cell-like phenotype, suggesting that emergence of resistance to AR-targeted therapy may be associated with loss of AR signaling and gain of stemness. In the present mini-review, we first discuss PCa from the perspective of an abnormal organ with increasingly deregulated differentiation, and discuss the role of AR signaling during PCa progression. We then focus on the relationship between prostate cancer stem cells (PCSCs) and AR signaling. We further elaborate on the current methods of using transcriptome-based stemness-enriched signature to evaluate the degree of oncogenic dedifferentiation (cancer stemness) in pan-cancer datasets, and present the clinical significance of scoring transcriptome-based stemness across the spectrum of PCa development. Our discussions highlight the importance to evaluate the dynamic changes in both stem cell-like features (stemness score) and AR signaling activity across the PCa spectrum.