It takes two to tango, a dance between the cells of origin and cancer stem cells in the Drosophila larval brain.
It takes two to tango, a dance between the cells of origin and cancer stem cells in the Drosophila larval brain.
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DOI：
10.1016/j.semcdb.2014.03.006
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发表时间：
2014-04
影响因子：
7.3
通讯作者：
Lee CY
中科院分区：
文献类型：
--
作者：
Janssens DH;Lee CY
在恶性转化过程中，原始细胞产生癌症干细胞，这些干细胞具有进行无限轮自我更新分裂的能力，在产生更多肿瘤细胞的同时再生自己。在正常组织中，无限的自我更新能力是干细胞所独有的，它不对称地分裂以产生更多受限的祖细胞。越来越多的证据表明，干细胞后代自我更新机制的失调可能导致肿瘤发生，但它如何影响所产生的肿瘤的性质仍不清楚。果蝇幼虫脑中的II型神经干细胞（成神经细胞）谱系的研究已经确定了一个调节级联，通过限制它们对自我更新机制的反应来促进对祖细胞身份的承诺。脑肿瘤（Brat）和Numb通过不对称地消除自我更新因子的活性来启动这种级联反应。随后，耳罩（Erm）和SWI/SNF复合物稳定地限制祖细胞响应自我更新机制的再激活的能力。总之，这一级联程序的祖细胞进行有限轮的分裂，产生排他性的分化后代。在这里，我们审查如何在这个级联缺陷导致肿瘤的启动和如何抑制自我更新机制可能是一个有效的策略，以阻止CSC的扩展。
During malignant transformation the cells of origin give rise to cancer stem cells which possess the capacity to undergo limitless rounds of self-renewing division, regenerating themselves while producing more tumor cells. Within normal tissues, a limitless self-renewal capacity is unique to the stem cells, which divide asymmetrically to produce more restricted progenitors. Accumulating evidence suggests that misregulation of the self-renewal machinery in stem cell progeny can lead to tumorigenesis, but how it influences the properties of the resulting tumors remains unclear. Studies of the type II neural stem cell (neuroblast) lineages in the Drosophila larval brain have identified a regulatory cascade that promotes commitment to a progenitor cell identity by restricting their response to the self-renewal machinery. Brain tumor (Brat) and Numb initiate this cascade by asymmetrically extinguishing the activity of the self-renewal factors. Subsequently, Earmuff (Erm) and the SWI/SNF complex stably restrict the competence of the progenitor cell to respond to reactivation of self-renewal mechanisms. Together, this cascade programs the progenitor cell to undergo limited rounds of division, generating exclusive differentiated progeny. Here we review how defects in this cascade lead to tumor initiation and how inhibiting the self-renewal mechanisms may be an effective strategy to block CSC expansion.