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整合素 α5β1,即纤维连接蛋白受体,作为实体瘤中一个有意义的治疗靶点。

Integrin α5β1, the Fibronectin Receptor, as a Pertinent Therapeutic Target in Solid Tumors.

机构信息

UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Tumoral Signaling and Therapeutic Targets, Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch, France.

出版信息

Cancers (Basel). 2013 Jan 15;5(1):27-47. doi: 10.3390/cancers5010027.

Abstract

Integrins are transmembrane heterodimeric proteins sensing the cell microenvironment and modulating numerous signalling pathways. Changes in integrin expression between normal and tumoral cells support involvement of specific integrins in tumor progression and aggressiveness. This review highlights the current knowledge about α5β1 integrin, also called the fibronectin receptor, in solid tumors. We summarize data showing that α5β1 integrin is a pertinent therapeutic target expressed by tumoral neovessels and tumoral cells. Although mainly evaluated in preclinical models, α5β1 integrin merits interest in particular in colon, breast, ovarian, lung and brain tumors where its overexpression is associated with a poor prognosis for patients. Specific α5β1 integrin antagonists will be listed that may represent new potential therapeutic agents to fight defined subpopulations of particularly aggressive tumors.

摘要

整合素是一种跨膜异二聚体蛋白,能够感知细胞微环境并调节多种信号通路。正常细胞和肿瘤细胞之间整合素表达的变化支持特定整合素参与肿瘤的进展和侵袭。这篇综述强调了目前关于α5β1 整合素(也称为纤维连接蛋白受体)在实体瘤中的认识。我们总结了表明α5β1 整合素是肿瘤新生血管和肿瘤细胞表达的一个相关治疗靶点的数据。尽管主要在临床前模型中进行评估,但α5β1 整合素在结肠癌、乳腺癌、卵巢癌、肺癌和脑癌等肿瘤中特别值得关注,因为其过表达与患者预后不良相关。我们将列出特定的α5β1 整合素拮抗剂,这些拮抗剂可能代表新的潜在治疗药物,用于对抗特定侵袭性肿瘤的特定亚群。

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本文引用的文献

1
Integrin trafficking at a glance.整合素运输一览。
J Cell Sci. 2012 Aug 15;125(Pt 16):3695-701. doi: 10.1242/jcs.095810.
4
Negative regulators of integrin activity.整合素活性的负调控因子。
J Cell Sci. 2012 Jul 15;125(Pt 14):3271-80. doi: 10.1242/jcs.093641. Epub 2012 Jul 20.
8
Integrins as therapeutic targets.整合素作为治疗靶点。
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