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癌症中的干细胞转录因子 NANOG——永恒的青春是诅咒吗?

Stem cell transcription factor NANOG in cancers--is eternal youth a curse?

机构信息

a Department of Pathology , The University of Hong Kong , Hong Kong Special Administrative Region , People's Republic of China.

出版信息

Expert Opin Ther Targets. 2016;20(4):407-17. doi: 10.1517/14728222.2016.1112791. Epub 2015 Dec 4.

Abstract

INTRODUCTION

Targeting cancer stem cells can be a more effective approach to treat cancer. NANOG is one of the key factors for maintaining the self-renewal ability and pluripotency of stem cells, including cancer stem cells. Overexpression of NANOG has been observed in various human malignancies. Several reports have suggested that NANOG contributes to carcinogenesis by initiating and preserving cancer stem cells. It is obvious that NANOG is also involved in establishing other hallmarks of cancer such as uncontrolled cell growth, chemoresistance, metastasis, and immune evasion.

AREAS COVERED

This review will discuss the molecular properties and oncogenic roles of NANOG. The idea of using agents that inhibit the transcription factor to treat cancer is presented. Interfering with NANOG-mediated transcriptions using small interfering RNA, transcription factor decoy, genome editing, and small-molecule inhibitors may provide novel strategies to target cancer stem cells.

EXPERT OPINION

As a pivotal controller in cancer stem cell maintenance and a positive regulator of various oncogenic pathways, NANOG may be an important target for cancer therapy. However, as a transcription factor, it is inherently difficult to target by pharmacological means. Novel approaches need to be explored before the inhibition of NANOG can be applied in a clinical setting.

摘要

简介

针对癌症干细胞可能是治疗癌症的更有效方法。NANOG 是维持干细胞(包括癌症干细胞)自我更新能力和多能性的关键因素之一。在各种人类恶性肿瘤中都观察到 NANOG 的过表达。有几项报道表明,NANOG 通过启动和维持癌症干细胞来促进癌变。显然,NANOG 也参与了建立癌症的其他标志,如失控的细胞生长、化疗耐药性、转移和免疫逃逸。

涵盖领域

这篇综述将讨论 NANOG 的分子特性和致癌作用。提出了使用抑制转录因子的药物治疗癌症的想法。使用小干扰 RNA、转录因子诱饵、基因组编辑和小分子抑制剂干扰 NANOG 介导的转录,可能为靶向癌症干细胞提供新的策略。

专家意见

作为癌症干细胞维持的关键控制器和各种致癌途径的正调节剂,NANOG 可能是癌症治疗的重要靶点。然而,作为一种转录因子,用药理学方法靶向它本身就很困难。在抑制 NANOG 能够在临床环境中应用之前,需要探索新的方法。

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