Metabolic Codependencies in the Tumor Microenvironment.

文献信息

DOI	10.1158/2159-8290.CD-20-1211
PMID	33504580
期刊	Cancer discovery
影响因子	33.3
JCR 分区	Q1
发表年份	2021
被引次数	174
关键词	代谢重编程, 肿瘤微环境, 内源性信号, 外源性信号, 代谢调节
文献类型	Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review
ISSN	2159-8274
页码	1067-1081
期号	11(5)
作者	Prasenjit Dey, Alec C Kimmelman, Ronald A DePinho

一句话小结

本研究综述了驱动癌细胞代谢重编程的内在和外在机制，发现癌细胞内的致癌改变与宿主细胞因子共同作用，调节代谢途径。该研究强调，靶向代谢途径需考虑癌症基因型和肿瘤微环境，以提高治疗效果。

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代谢重编程 · 肿瘤微环境 · 内源性信号 · 外源性信号 · 代谢调节

摘要

代谢重编程使癌细胞能够生长、增殖和存活。这种重编程是由癌细胞内的致癌改变与作用于肿瘤微环境中癌细胞的宿主细胞因子的共同作用驱动的。癌细胞内在机制激活信号转导成分，这些成分要么直接增强代谢酶的活性，要么上调转录因子，从而增加代谢调节因子的表达。外源性信号机制涉及宿主来源的因子，这些因子进一步促进和放大癌细胞中的代谢重编程。本文综述了驱动肿瘤微环境中癌症代谢的内在和外在机制，以及如何将这些机制作为治疗靶点。意义：癌细胞的代谢重编程是内在和外在因素的汇聚信号的结果。内在信号维持基线代谢状态，而外在信号则根据代谢物的可用性和细胞的需求来微调代谢过程。因此，成功靶向代谢途径需要基于癌症的基因型、肿瘤微环境组成和组织位置的细致方法。

英文摘要

Metabolic reprogramming enables cancer cell growth, proliferation, and survival. This reprogramming is driven by the combined actions of oncogenic alterations in cancer cells and host cell factors acting on cancer cells in the tumor microenvironment. Cancer cell-intrinsic mechanisms activate signal transduction components that either directly enhance metabolic enzyme activity or upregulate transcription factors that in turn increase expression of metabolic regulators. Extrinsic signaling mechanisms involve host-derived factors that further promote and amplify metabolic reprogramming in cancer cells. This review describes intrinsic and extrinsic mechanisms driving cancer metabolism in the tumor microenvironment and how such mechanisms may be targeted therapeutically. SIGNIFICANCE: Cancer cell metabolic reprogramming is a consequence of the converging signals originating from both intrinsic and extrinsic factors. Intrinsic signaling maintains the baseline metabolic state, whereas extrinsic signals fine-tune the metabolic processes based on the availability of metabolites and the requirements of the cells. Therefore, successful targeting of metabolic pathways will require a nuanced approach based on the cancer's genotype, tumor microenvironment composition, and tissue location.

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主要研究问题

核心洞察

研究背景和目的

癌细胞的代谢重编程是其生长、增殖和存活的关键。这一过程受癌细胞内源性变化与宿主细胞因素的共同作用驱动。了解这些机制对于开发新的癌症治疗策略具有重要意义。本综述旨在探讨肿瘤微环境中驱动癌细胞代谢的内源性和外源性机制，并讨论如何针对这些机制进行治疗。

主要方法/材料/实验设计

本研究综述了内源性和外源性信号在癌细胞代谢重编程中的作用，主要包括以下几个方面：

内源性机制：
- 癌细胞内的信号转导组分被激活，直接增强代谢酶的活性。
- 转录因子的上调导致代谢调节因子的表达增加。
外源性机制：
- 宿主来源的因子进一步促进并放大癌细胞的代谢重编程。

以下是研究的技术路线图：

关键结果和发现

癌细胞的代谢重编程是内源性和外源性信号共同作用的结果。
内源性信号维持了基础代谢状态，而外源性信号则根据代谢物的可用性和细胞需求微调代谢过程。
不同类型的癌症可能对代谢干预有不同的反应，这与其基因型和肿瘤微环境的组成密切相关。

主要结论/意义/创新性

成功靶向癌细胞的代谢通路需要基于癌症的基因型、肿瘤微环境的组成和组织位置的细致策略。这一发现强调了在癌症治疗中综合考虑内源性和外源性因素的重要性，为未来的治疗方案提供了新的视角和方向。

研究局限性和未来方向

本综述未能深入探讨不同癌症类型之间代谢重编程的具体差异，未来的研究应关注这一领域。
对于如何有效靶向代谢途径，仍需更多临床试验和基础研究的支持。
未来研究可以进一步探索宿主细胞因素与癌细胞代谢之间的复杂相互作用，以发现新的治疗靶点。

参考文献

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... (164 更多篇文献)

Metabolic Codependencies in the Tumor Microenvironment. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

参考文献 ​

引用本文的文献 ​