Stem cells, immortality, and the evolution of metastatic properties in breast cancer: telomere maintenance mechanisms and metastatic evolution.
Stem cells, immortality, and the evolution of metastatic properties in breast cancer: telomere maintenance mechanisms and metastatic evolution.
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DOI：
10.20517/2394-4722.2019.15
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发表时间：
2019-01-01
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影响因子：
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通讯作者：
Schiemann, William P
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作者：
Robinson, Nathaniel J;Taylor, Derek J;Schiemann, William P
乳腺癌是世界各地女性癌症相关死亡的最重要原因。绝大多数乳腺癌相关死亡源于转移，这仍然是一种无法治愈的疾病状态。转移是克隆进化的结果，这些克隆具有传播和定植远处器官所需的阴险特性。这些克隆群体是乳腺癌干细胞 (CSC) 的后代，它们也负责它们的长期维持和持续进化。端粒赋予细胞寿命，当细胞主动延长时，寿命可以延长，就像癌症干细胞中发生的那样。因此，端粒结构的变化有助于促进CSC的存活和随后的转移进化。端粒维持机制（TMM）的选择不仅对CSC的生存和进化具有重要影响，而且对它们协调编排转移级联的各种信号通路也有重要影响。因此，针对端粒维持机制可能为转移性乳腺癌的治疗带来福音。在这里，我们回顾了两种主要的 TMM 及其在干细胞和转移性乳腺癌细胞发育中所发挥的作用。我们还强调了当前和未来在临床环境中针对这些机制以减轻转移性乳腺癌的方法。
Breast cancer is the most significant cause of cancer-related death in women around the world. The vast majority of breast cancer-associated mortality stems from metastasis, which remains an incurable disease state. Metastasis results from evolution of clones that possess the insidious properties required for dissemination and colonization of distant organs. These clonal populations are descended from breast cancer stem cells (CSCs), which are also responsible for their prolonged maintenance and continued evolution. Telomeres impose a lifespan on cells that can be extended when they are actively elongated, as occurs in CSCs. Thus, changes in telomere structure serve to promote the survival of CSCs and subsequent metastatic evolution. The selection of telomere maintenance mechanism (TMM) has important consequences not only for CSC survival and evolution, but also for their coordination of various signaling pathways that choreograph the metastatic cascade. Targeting the telomere maintenance machinery may therefore provide a boon to the treatment of metastatic breast cancer. Here we review the two major TMMs and the roles they play in the development of stem and metastatic breast cancer cells. We also highlight current and future approaches to targeting these mechanisms in clinical settings to alleviate metastatic breast cancers.