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Notch signaling pathway

内分泌

关键词内分泌 临床研究术语 信号通路

词汇介绍

拓展阅读

解析

notch   英 /nɒtʃ/   美 /nɑːtʃ/

释    义   n. 刻痕,凹口;等级;峡谷

               vt. 赢得;用刻痕计算;在…上刻凹痕

同根词   notched adj. 有凹口的;有缺口的;有锯齿状的

例    句   It was time to step it up a notch and get my body in shape it deserves.是时候让我的身材更上一层楼了。

 

signaling   英 /'sɪɡnəlɪŋ/

释    义   n. 发信号;打信号

同根词   signal adj. 显著的;作为信号的

               sign n. 迹象;符号;记号;手势

               signed v. 署名;写下;预示;示意(sign的过去分词)

               sign vi. 签署;签名

               sign vt. 签署;示意

例    句   This and our other findings indicate that estrogen directly affects the brain, perhaps by interfering with brain signaling molecules.这和我们其他的观察都暗示了雌激素会直接影响大脑,也许它会妨碍大脑的信号分子。

 

pathway   英 /ˈpɑːθweɪ/   美 /ˈpæθweɪ/

释    义   n. 路,道;途径,路径;神经通路

例    句   You therefore have to find out which pathway is crucial in a cancer before you can make the drug.因此,医生须在制造药物之前找出在某一癌症中起关键作用的分子途径。

概述

Notch信号通路是存在于大多数动物系统的一种高度保守的细胞信号。哺乳动物拥有四个不同的缺口受体,分别称为NOTCH1,NOTCH2,NOTCH3和NOTCH4。Notch受体是单程跨膜受体蛋白。它是由大的细胞外部分组成的杂合寡聚物,与钙依赖性非共价缔合与由较小的细胞外区域,单个跨膜通道和较小的细胞内区域组成的较小的缺口蛋白相互作用。Notch信号在神经发生过程中促进增殖信号,而Numb抑制其活性以促进神经分化,它在调节胚胎发育中起主要作用。 作

Notch Signaling in the Tumor Microenvironment 复制标题

肿瘤微环境中的Notch信号

发表时间:2018-10-15

影响因子:23.9

作者: Olivier Meurette

期刊:Cancer Cell

The tumor is an organ-like structure that results from the co-evolution of  malignant cells and their direct environment. The tumor microenvironment (TME) encompasses all the structures that are recruited to this organ: vascular vessels, immune infiltrates, fibroblasts, and the  extracellular matrix. Tumor progression, resistance to therapy, invasion, and metastasis are emergent properties of the bidirectional interactions between the cancer cells and the TME. Understanding the co-evolution of the cancer cells and their physical and cellular environment is crucial for the development of new efficient therapies. The crosstalk between the cancer cells and their environment involve reciprocal juxtacrine and paracrine signaling using many different pathways. Among them, the Notch signaling pathway is an important pathway that is recognized as a major actor both in the cancer cells and in each of the components of the TME. The role of the Notch signaling pathway in cancer cells either acting in an oncogenic or a tumor-suppressive manner has been extensively reviewed. However, an increasing number of studies show the role of Notch signaling in regulating, through juxtacrine or paracrine signaling, the TME. The aim of this review is thus to point the perspective toward the role of Notch signaling in the TME in which each compartment expresses a variety of Notch ligands and receptors. Notch signaling is induced at cell-cell contact between a signal-sending and a signal-receiving cell. Notch juxtacrine signaling can therefore regulate  heterotypic interactions between the stroma and the tumor and vice versa. These interactions have been shown to regulate many aspects of tumor biology, such as  angiogenesis, cancer stem cell maintenance, the immune infiltrate, or resistance to therapy. Furthermore, Notch activation also mediates secretion of numerous molecules that non-autonomously affect cells from the TME. Studying the implication of Notch signaling in the TME shows that Notch is involved in both pro- and anti-tumoral effects in the different populations composing the tumor. We therefore argue that, both from a basic point of view and in order to design anti-Notch therapeutics, an exhaustive look at the TME is required. The aim of this review is thus to explore the involvement of Notch signaling in every component of the TME and discuss the impact of these mechanisms from a therapeutic perspective.

译文

肿瘤是一种器官样结构,是恶性细胞与其直接环境共同进化的结果。肿瘤微环境(TME)包含了所有进入该器官的结构:血管、免疫浸润、成纤维细胞和细胞外基质。肿瘤的进展、对治疗的抵抗、侵袭和转移是肿瘤细胞与TME双向相互作用的新特性。了解癌细胞及其物理和细胞环境的共同进化对于开发新的有效疗法至关重要。癌细胞与其周围环境之间的串扰涉及到使用许多不同途径的交叉旁吖啶和旁分泌信号。其中Notch信号通路是一条重要的信号通路,被认为是癌细胞和TME各组成部分的主要作用因子。Notch信号通路在癌细胞中的作用无论是以致癌还是抑癌的方式已经被广泛的综述。然而,越来越多的研究表明Notch信号在通过旁吖啶或旁分泌信号调节TME中的作用。因此,本综述的目的是指出Notch信号在TME中的作用,在TME中,每个细胞室表达多种Notch配体和受体。Notch信号在信号发送和信号接收单元之间的单元-单元接触处被诱导。因此Notch-juxtacrine信号可以调节基质和肿瘤之间的异型相互作用,反之亦然。这些相互作用已经被证明可以调节肿瘤生物学的许多方面,如血管生成、肿瘤干细胞维持、免疫浸润或对治疗的抵抗。此外,Notch激活还介导大量分子的分泌,这些分子非自主地影响来自TME的细胞。研究Notch信号在TME中的意义表明,Notch在构成肿瘤的不同人群中参与促肿瘤和抗肿瘤作用。因此,我们认为,无论是从基本观点还是为了设计抗缺口疗法,都需要对TME进行详尽的研究。因此,本综述旨在探讨Notch信号在TME各成分中的作用,并从治疗的角度探讨这些机制的影响。