Metabolic Reprogramming by the PI3K-Akt-mTOR Pathway in Cancer
Metabolic Reprogramming by the PI3K-Akt-mTOR Pathway in Cancer
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DOI：
10.1007/978-3-319-42118-6_3
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发表时间：
2016-01-01
期刊：
影响因子：
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通讯作者：
Cantley, Lewis C.
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文献类型：
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作者：
Lien, Evan C.;Lyssiotis, Costas A.;Cantley, Lewis C.
在过去的十年中，人们对阐明癌细胞中代谢如何改变以及如何将这种依赖性作为治疗目标的兴趣重新抬头。这项研究的核心是这样一个概念，即代谢途径在癌细胞中被重新编程，将营养物质转移到合成代谢过程中，以促进生长和增殖。重要的是，生理细胞信号传导机制通常严格调节细胞获得和利用营养物质的能力，构成转化的基本障碍。这一障碍通常被细胞信号传导中的畸变所克服，细胞信号传导通过使癌细胞能够以细胞自主的方式做出关键的细胞决定来驱动肿瘤发病机制。人类癌症中最常改变的途径之一是PI 3 K-Akt-mTOR信号传导途径。在这里，我们描述了这种信号网络负责控制细胞代谢的机制。通过翻译后调节和转录程序的诱导，PI 3 K-Akt-mTOR途径以最适合于支持癌细胞的增强生长和增殖的方式协调多种营养物（包括葡萄糖、谷氨酰胺、核苷酸和脂质）的摄取和利用。这些调节机制说明了癌症中的代谢变化如何与驱动肿瘤发生和进展的致癌信号通路密切相关。
In the past decade, there has been a resurgence of interest in elucidating how metabolism is altered in cancer cells and how such dependencies can be targeted for therapeutic gain. At the core of this research is the concept that metabolic pathways are reprogrammed in cancer cells to divert nutrients toward anabolic processes to facilitate enhanced growth and proliferation. Importantly, physiological cellular signaling mechanisms normally tightly regulate the ability of cells to gain access to and utilize nutrients, posing a fundamental barrier to transformation. This barrier is often overcome by aberrations in cellular signaling that drive tumor pathogenesis by enabling cancer cells to make critical cellular decisions in a cell-autonomous manner. One of the most frequently altered pathways in human cancer is the PI3K-Akt-mTORsignaling pathway. Here, we describe mechanisms by which this signaling network is responsible for controlling cellular metabolism. Through both the post-translational regulation and the induction of transcriptional programs, the PI3K-Akt-mTOR pathway coordinates the uptake and utilization of multiple nutrients, including glucose, glutamine, nucleotides, and lipids, in a manner best suited for supporting the enhanced growth and proliferation of cancer cells. These regulatory mechanisms illustrate how metabolic changes in cancer are closely intertwined with oncogenic signaling pathways that drive tumor initiation and progression.