Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K
Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K
复制标题
DOI：
10.1007/s11033-015-3858-x
复制
发表时间：
2015-04-01
影响因子：
2.8
通讯作者：
Karagiannis, Tom C.
中科院分区：
文献类型：
--
作者：
Courtnay, Rupert;Ngo, Darleen C.;Karagiannis, Tom C.
与正常的非恶性细胞相比，癌细胞已被证明具有改变的代谢。瓦尔堡效应描述了一种现象，其中癌细胞优先通过糖酵解代谢葡萄糖，产生乳酸作为最终产物，尽管存在氧气。这一现象最早由奥托·瓦尔堡在20世纪20年代描述，并作为一个有争议的理论重新浮出水面，有支持和反对的论点。瓦尔堡效应的生物化学方面通过提供细胞生长的生物学要求，概述了对癌细胞增殖原因的有力解释。研究表明，磷酸肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PI 3 K/Akt/mTOR）以及缺氧诱导因子-1（HIF-1）等通路是糖酵解、肿瘤代谢和癌细胞增殖的中心调节因子。研究表明，PI 3 K信号通路在许多细胞过程中发挥作用，如代谢、炎症、细胞存活、运动和癌症进展。在本文中，描述了PI 3 K途径的细胞方面，以及HIF对癌细胞代谢的影响。HIF-1激活与血管生成、红细胞生成和有氧糖酵解中关键酶的调节有关，从而调节瓦尔堡效应所需的关键过程。在这篇综述中，我们讨论了瓦尔堡效应的分子方面，特别强调HIF-1和PI 3 K通路的作用。
Cancer cells have been shown to have altered metabolism when compared to normal non-malignant cells. The Warburg effect describes a phenomenon in which cancer cells preferentially metabolize glucose by glycolysis, producing lactate as an end product, despite being the presence of oxygen. The phenomenon was first described by Otto Warburg in the 1920s, and has resurfaced as a controversial theory, with both supportive and opposing arguments. The biochemical aspects of the Warburg effect outline a strong explanation for the cause of cancer cell proliferation, by providing the biological requirements for a cell to grow. Studies have shown that pathways such as phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) as well as hypoxia inducible factor-1 (HIF-1) are central regulators of glycolysis, cancer metabolism and cancer cell proliferation. Studies have shown that PI3K signaling pathways have a role in many cellular processes such as metabolism, inflammation, cell survival, motility and cancer progression. Herein, the cellular aspects of the PI3K pathway are described, as well as the influence HIF has on cancer cell metabolism. HIF-1 activation has been related to angiogenesis, erythropoiesis and modulation of key enzymes involved in aerobic glycolysis, thereby modulating key processes required for the Warburg effect. In this review we discuss the molecular aspects of the Warburg effect with a particular emphasis on the role of the HIF-1 and the PI3K pathway.