Promotion of cancer cell stemness by Ras.
Promotion of cancer cell stemness by Ras.
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DOI：
10.1042/bst20200964
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发表时间：
2021-02-26
影响因子：
3.9
通讯作者：
Abankwa D
中科院分区：
文献类型：
--
作者：
Chippalkatti R;Abankwa D
癌症干细胞(CSC)可能是最相关和最难以捉摸的癌细胞群体，因为它们具有种植新肿瘤的出色能力。看似合理的是，高度突变的癌症基因，如KRAS，在功能上与促成茎性状出现的过程有关。在这篇综述中，我们将对致癌RAS的茎驱动活性的证据进行综述。这种活性似乎因RAS亚型不同而不同，高度突变的KRAS具有特别深刻的影响。除了Wnt和Hedgehog(HH)等已建立的茎干途径外，MAPK途径的精确、依赖于细胞周期的编排似乎在这种情况下传递RAS的激活。我们将研究K-RAS4B(以下简称K-RAS)的非典型活性如何通过其交易伴侣钙调蛋白和PDE6D/PDEδ来实现。两者都动态地定位于与细胞命运决定密切相关的细胞机制，如初级纤毛和中心体。因此，可以推测致癌K-RAS干扰了细胞分化所必需的基本极化信号和不对称分配过程。
Cancer stem cells (CSC) may be the most relevant and elusive cancer cell population, as they have the exquisite ability to seed new tumors. It is plausible, that highly mutated cancer genes, such as KRAS, are functionally associated with processes contributing to the emergence of stemness traits. In this review, we will summarize the evidence for a stemness driving activity of oncogenic Ras. This activity appears to differ by Ras isoform, with the highly mutated KRAS having a particularly profound impact. Next to established stemness pathways such as Wnt and Hedgehog (Hh), the precise, cell cycle dependent orchestration of the MAPK-pathway appears to relay Ras activation in this context. We will examine how non-canonical activities of K-Ras4B (hereafter K-Ras) could be enabled by its trafficking chaperones calmodulin and PDE6D/PDEδ. Both dynamically localize to the cellular machinery that is intimately linked to cell fate decisions, such as the primary cilium and the centrosome. Thus, it can be speculated that oncogenic K-Ras disrupts fundamental polarized signaling and asymmetric apportioning processes that are necessary during cell differentiation.