PI3K/AKT/mTOR Pathway in Angiogenesis.
PI3K/AKT/mTOR Pathway in Angiogenesis.
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DOI：
10.3389/fnmol.2011.00051
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发表时间：
2011
影响因子：
4.8
通讯作者：
Maity A
中科院分区：
文献类型：
--
作者：
Karar J;Maity A
磷脂酰肌醇3-激酶(PI3K)/AKT/哺乳动物雷帕霉素靶标(MTOR)通路在大多数人类癌症中被激活。已知该途径在多种细胞功能中发挥关键作用，包括增殖、黏附、迁移、侵袭、代谢和生存，但在目前的综述中，我们重点介绍它在血管生成中的作用。PI3K的激活可能通过RAS突变、磷酸酶和紧张素同源物(PTEN)的丢失或通过生长因子受体(如表皮生长因子受体)的表达增加而发生。PI3K通路与血管生成之间存在联系。缺氧导致缺氧诱导因子-1α的稳定，是肿瘤细胞增加血管内皮生长因子产生的主要刺激因素。然而，肿瘤细胞中PI3K/AKT通路的激活也可以通过缺氧诱导因子1(HIF-1)依赖和独立的机制增加血管内皮生长因子的分泌。PI3K/AKT通路还调节其他血管生成因子的表达，如一氧化氮和血管生成素。许多针对PI3K/AKT/mTOR通路的抑制剂已经被开发出来，这些药物被证明可以减少VEGF的分泌和血管生成。这些抑制物对肿瘤血管的影响可能很难预测。肿瘤的血管系统异常，导致血流迟缓和间质血压升高，这可以通过高水平的血管内皮生长因子持续存在。因此，在某些肿瘤中，降低血管内皮生长因子的表达可以矛盾地导致血管正常化和改善血流。除了在癌症中的重要性外，PI3K通路在发育过程中对正常血管的形成也起着至关重要的作用。带有PI3K的p110α催化亚基的胚胎会出现血管缺陷。血管内皮细胞受到血管内皮细胞的刺激后，PI3K通路被激活，这对细胞的迁移起着重要的作用。AKT1的持续内皮激活已被证明可以诱导结构异常的血管的形成，这些血管重现了肿瘤血管的异常。因此，PI3K通路在调节正常组织和肿瘤中的血管生成方面起着重要的作用。
The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is activated in the majority of human cancers. This pathway is known to play a key role in numerous cellular functions including proliferation, adhesion, migration, invasion, metabolism, and survival, but in the current review we focus on its role in angiogenesis. PI3K activation may occur via RAS mutation, loss of phosphatase and tensin homolog (PTEN), or by increased expression of growth factor receptors such as epidermal growth factor receptor. There is a connection between the PI3K pathway and angiogenesis. Hypoxia leads to HIF-1α stabilization and is a major stimulus for increased vascular endothelial growth factor (VEGF) production by tumor cells. However, activation of the PI3K/AKT pathway in tumor cells can also increase VEGF secretion, both by hypoxia-inducible factor 1 (HIF-1) dependent and independent mechanisms. The PI3K/AKT pathway also modulates the expression of other angiogenic factors such as nitric oxide and angiopoietins. Numerous inhibitors targeting the PI3K/AKT/mTOR pathway have been developed, and these agents have been shown to decrease VEGF secretion and angiogenesis. The effect of these inhibitors on tumor vasculature can be difficult to predict. The vasculature of tumors is aberrant, leading to sluggish bloodflow and elevated interstitial blood pressure, which can be perpetuated by the high levels of VEGF. Hence, decreasing VEGF expression can paradoxically lead to vascular normalization and improved bloodflow in some tumors. In addition to its importance in cancer, the PI3K pathway also plays an essential role in the formation of normal blood vessels during development. Embryos with kinase-dead p110α catalytic subunit of PI3K develop vascular defects. Stimulation of endothelial cells by VEGF leads to activation of the PI3K pathway within these cells, which is important for cell migration. Sustained endothelial activation of AKT1 has been shown to induce the formation of structurally abnormal blood vessels that recapitulate the aberrations of tumor vessels. Hence, the PI3K pathway plays an important role in regulating angiogenesis both in normal tissues and in cancers.
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表皮生长因子受体抑制通过血管正常化调节微环境，从而提高化疗和放疗疗效。
影响因子：
3.7
作者：
Cerniglia, George J.;Pore, Nabendu;Tsai, Jeff H.;Schultz, Susan;Mick, Rosemarie;Choe, Regine;Xing, Xiaoman;Durduran, Turgut;Yodh, Arjun G.;Evans, Sydney M.;Koch, Cameron J.;Hahn, Stephen M.;Quon, Harry;Sehgal, Chandra M.;Lee, William M. F.;Maity, Amit
通讯作者：
Maity, Amit
DOI：
10.1083/jcb.200907135
发表时间：
2010-03-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cain RJ;Vanhaesebroeck B;Ridley AJ
通讯作者：
Ridley AJ
影响因子：
64.8
作者：
Dimmeler, S;Fleming, I;Zeiher, AM
通讯作者：
Zeiher, AM
影响因子：
5.6
作者：
Cascio, Sandra;Ferla, Rita;Russo, Antonio
通讯作者：
Russo, Antonio
DOI：
10.1073/pnas.041359198
发表时间：
2001-02-27
影响因子：
11.1
作者：
Fukumura, D;Gohongi, T;Jain, RK
通讯作者：
Jain, RK