Reduction in the requirement of oncogenic Ras signaling to activation of PI3K/AKT pathway during tumor maintenance
Reduction in the requirement of oncogenic Ras signaling to activation of PI3K/AKT pathway during tumor maintenance
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DOI：
10.1016/j.ccr.2005.10.014
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发表时间：
2005-11-01
期刊：
影响因子：
50.3
通讯作者：
Counter, CM
中科院分区：
文献类型：
--
作者：
Lim, KH;Counter, CM
虽然肿瘤会对RAS等癌基因上瘾，但肿瘤细胞所处的微环境在肿瘤发生过程中会发生变化；细胞最初被正常组织包围，后来又被肿瘤组织包围。因此，我们询问RAS是否在肿瘤发生的不同阶段通过相同的一组效应器发挥致癌作用。我们现在在人类细胞中表明，RAS效应通路MAPK、RaIGEF和PI3K是启动肿瘤生长所必需的。相反，一旦肿瘤形成，PI3K/AKT通路的激活取代了RAS，尽管其他效应器仍然独立于RAS被激活，推测是由肿瘤微环境建立时提供的因素所致。因此，随着肿瘤发生的进展，癌症对其启动的癌基因的依赖被降低到至少在RAS的情况下，PI3K/AKT途径。
While tumors become addicted to oncogenes like Ras, the microenvironment in which tumor cells reside changes during tumorigenesis; the cells are surrounded initially by normal tissue and later by tumor tissue. Hence, we asked if Ras exerts its oncogenic effects through the same set of effectors during different stages of tumorigenesis. We now show in human cells that the Ras effector pathways MAPK, RaIGEF, and PI3K are required to initiate tumor growth. Conversely, activation of the PI3K/AKT pathway replaced Ras once tumors formed, although other effectors were still activated independently of Ras, presumably by factors provided upon the establishment of a tumor microenvironment. Thus, as tumorigenesis progresses the addiction of cancers to their initiating oncogene is reduced to, at least in the case of Ras, the PI3K/AKT pathway.