共查询到17条相似文献,搜索用时 156 毫秒
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《实用药物与临床》2019,(10)
缺氧诱导因子(Hypoxia-inducible fact,HIF)为缺氧、炎症、代谢适应和肿瘤进展之间的重要交汇点,同时也参与纤维化的进展过程。Notch信号通路是一个在进化过程中高度保守的信号通路,广泛参与细胞的增殖、分化及凋亡过程,在恶性肿瘤的侵袭与转移等过程中发挥着重要作用。缺氧诱导的上皮间质转化(Epithelial-mesenchymal transition,EMT)需要功能性的Notch信号转导驱动EMT的过程。近年研究表明,细胞缺氧反应并不是单独的反应,而是与信号机制相交,例如Notch信号传导,这是在控制干细胞维持和分化的大多数细胞类型中操作的关键调节信号传导机制。本文讨论了关于Notch信号通路与细胞缺氧反应之间的交集以及Notch信号和缺氧在EMT相关疾病中的作用机制。 相似文献
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JAK/STAT通路参与细胞的增殖、分化和凋亡等过程,近年来的研究显示,其在胚胎发育、成年个体脑肿瘤、脑缺血及损伤后脑内神经干细胞增殖过程中发挥重要作用。Notch介导的信号通路广泛存在于所有已知动物细胞中,是调控神经干细胞增殖、分化的经典信号通路。两条通路形成一个整体网络调控着神经干细胞增殖分化,本文综述Notch通路与JAIL/STAT通路在神经干细胞增殖过程中各组分的相互联系,旨在从网络药理学角度为脑缺血后神经保护及调控神经干细胞增殖药物的开发提供基础理论支持。 相似文献
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摘要: Notch家族是多细胞生物发育过程中一类高度保守的、 十分重要的跨膜信号蛋白, 通过与相邻细胞之间的相互作用, 在细胞增殖、 分化、 凋亡中发挥着关键作用。调节性T细胞 (Treg) 及辅助性T细胞17 (Th17) 是目前发现的一类新型CD4+ T细胞亚群, 在生理状态下, 两者可通过分泌多种细胞因子来调节机体免疫的平衡。近年来, 越来越多的研究发现Notch信号通路通过调控Treg、 Th17细胞参与机体多种疾病的发生。本文就Notch信号通路在血液系统疾病、 自身免疫系统疾病等疾病中对Treg/Th17细胞调控机制的研究进展作一简要综述。 相似文献
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Targeting Of miR9/NOTCH1 Interaction Reduces Metastatic Behavior in Triple‐negative Breast Cancer
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Samira Mohammadi‐Yeganeh Ardalan Mansouri Mahdi Paryan 《Chemical biology & drug design》2015,86(5):1185-1191
Many reports have indicated deregulation of a variety of microRNAs (miRNAs) in human cancers. In this study, we appraised miR‐9 correlation with NOTCH1 involved in Notch signaling in metastatic breast cancer. The Notch signaling pathway has been approved to be associated with the development and progression of many human cancers, including breast cancer, but the precise mechanism has remained unknown. To the best of our knowledge, this is the first study that introduces miR‐9 and NOTCH1 correlation as an effective factor in breast cancer. We found that miR‐9 expression was decreased in MDA‐MB‐231 breast cancer cells compared with MCF‐10A normal breast cell line. However, NOTCH1 was upregulated in the metastatic breast cancer cells. Furthermore, luciferase assay revealed a significant inverse correlation between miR‐9 and NOTCH1. Overexpression of Notch signaling via Notch1 intracellular domain in MDA‐MB‐231 cell line was suppressed by lentiviruses expressing miR‐9. Taken together, the results obtained by MTT, flow cytometry, migration, and wound healing assays showed that it is possible to inhibit metastasis and induce pro‐apoptotic state by induction of miR‐9 expression in MDA‐MB‐231 cells but with no effect on cell proliferation. These results shows that miR‐9, by direct targeting of NOTCH1, can reveal a suppressor‐like activity in metastatic breast cancer cells. 相似文献
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Wnt信号通路在乳腺癌的发生发展中起重要作用,参与成体细胞的增殖分化和凋亡。β-catenin的异常表达是乳腺癌发生发展过程中的重要因子,这个过程可能是通过激活cyclin D1实现的。E-钙粘蛋白是关系乳腺癌发展与预后的关键因子,WIF1是Wnt通路中的抑癌基因,对肿瘤的发生发展起着重要作用。本文从Wnt通路组成、Wnt通路的抑制剂和调控及其与乳腺癌的关系作一综述。 相似文献
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The Notch signaling pathway is a highly conserved developmental pathway, which plays a critical role in cell-fate decision, tissue patterning and morphogenesis. There is increasing evidence that this pathway is dysregulated in a variety of malignancies, and can behave as either an oncogene or a tumor suppressor depending upon cell context. This review highlights the current evidence for aberration of the Notch signaling pathway in a wide range of tumors from hematological cancers, such as leukemia and lymphoma through to skin, breast, lung, pancreas, colon and brain tumors. It proposes that the Notch signaling pathway may represent novel therapeutic targets and will be a welcome asset to the cancer therapeutic arena. 相似文献
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The Notch pathway and the endocrine system constitute two key biological signaling mechanisms, responsible for cell-to-cell communication between adjacent cells and long-distance hormonal signals respectively. They play central roles during the development of higher eukaryotic organisms but they also take part in the regulation of many aspects of adult physiology and homeostasis. The contribution of defects in the normal transmission of hormone-dependent signals to the development of endocrine cancers has been widely analyzed and the knowledge derived from these studies has allowed us to develop many successful therapeutic strategies. However, in many cases these hormonal treatments become ineffective despite the fact that cancer cells maintain normal expression levels of wild-type hormone nuclear receptors. Less is known about the involvement of altered Notch signaling in the origin and progression of cancer, although there is clear evidence indicating that deregulation of Notch activity occurs in several types of tumors, including highly prevalent hormone-dependent types of cancer such as breast, ovarian and prostate cancer. This review will summarize accumulating data suggesting that Notch signaling plays a key role in the control of proliferation, differentiation and survival of prostate epithelial cells. Notch signals are required for normal prostate development and homeostasis, and abnormalities in Notch signaling may be critical during the development of prostate cancer. We will also discuss the possible oncogenic role for alterations in the crosstalk mechanisms between Notch and androgen-dependent signals during tumorigenesis in the prostate and how they could influence the outcome of anti-cancer hormonal treatments. 相似文献
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Lauth M Toftgård R 《Current opinion in investigational drugs (London, England : 2000)》2007,8(6):457-461
As with other developmentally important signaling pathways such as Wnt, TGF or Notch signaling, the Hedgehog (Hh) pathway has been shown to play an important role in the formation of several tumor types, including pancreas, prostate, skin and brain cancer. As the prognosis for some of these cancers is still poor, the Hh pathway may represent a novel drug target with high therapeutic potential. This review describes the mechanisms of signal transduction of the Hh pathway and the alterations that lead to tumor formation, highlighting the several drug development programs that are aimed at correcting these alterations. 相似文献
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《Expert opinion on therapeutic targets》2013,17(9):1095-1103
The Hedgehog (Hh) signalling pathway is a highly conserved developmental pathway, which plays critical roles in patterning of the embryo through epithelial to mesenchymal signalling and the maintenance of stem cells in the adult organism. There is increasing evidence that this pathway is dysregulated in many malignancies, including breast cancer. While there has been a significant decrease in mortality from breast cancer, a number of treatment challenges remain, particularly in those tumours which develop resistance to endocrine-based therapy, or which lack expression of hormone or c-erbB2/HER2 receptors. Therapeutic manipulation of the Hh pathway as a potential cancer therapy is attracting great interest, with preclinical studies and clinical trials underway in a range of malignancies. This review highlights important recent developments that affect the potential of the Hh pathway as a novel therapeutic target in early breast cancer. 相似文献