Androgen regulation of epithelial-mesenchymal transition in prostate tumorigenesis.
Androgen regulation of epithelial-mesenchymal transition in prostate tumorigenesis.
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DOI：
10.1586/eem.11.32
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发表时间：
2011-05
影响因子：
3.2
通讯作者：
Kyprianou N
中科院分区：
文献类型：
--
作者：
Matuszak EA;Kyprianou N
前列腺癌患者的死亡率归因于癌细胞扩散到前列腺外的区域，以及目前的治疗策略无法有效阻断转移的进展。了解有助于恶性细胞传播和转移的细胞机制对于产生有效的治疗方式以改善患者存活率同时对抗治疗耐药性至关重要。近年来，由于越来越多的证据表明这种发育保守过程在肿瘤发生中的作用，上皮-间充质转化（EMT）现象受到了相当大的关注。在肿瘤的侵袭性边缘处的癌细胞在它们从微环境接收的背景信号（诸如TGF-β）的影响下经历EMT。从发育研究中还发现EMT诱导是可逆的;因此，在去除EMT诱导信号后，细胞偶尔会通过间充质-上皮转化过程恢复到其细胞祖先的上皮状态。本文讨论了目前的证据支持EMT及其逆转过程，间充质-上皮转化，在前列腺癌转移进展到晚期疾病和雄激素信号转导的参与，其调节去势抵抗性前列腺癌的发展中的核心作用。
Prostate cancer patient mortality is ascribed to the spread of cancerous cells to areas outside the prostate gland and the inability of current treatment strategies to effectively block progression to metastasis. Understanding the cellular mechanisms contributing to the dissemination of malignant cells and metastasis is critically significant to the generation of effective therapeutic modalities for improved patient survival while combating therapeutic resistance. In recent years, the phenomenon of epithelial–mesenchymal transitions (EMTs) has received considerable attention due to accumulating evidence indicating a role for this developmentally conserved process in tumorigenesis. Cancer cells at the invasive edges of tumors undergo EMT under the influence of contextual signals that they receive from the microenvironment, such as TGF-β. Also derived from developmental studies is the fact that EMT induction is reversible; thus, upon removal of EMT-inducing signals, cells occasionally revert to the epithelial state of their cellular ancestors via the process of mesenchymal–epithelial transition. This article discusses the current evidence supporting a central role for EMT and its reverse process, mesenchymal–epithelial transition, in the metastatic progression of prostate cancer to advanced disease and the involvement of androgen signaling in its regulation towards the development of castration-resistant prostate cancer.