摘要
上皮间质转分化 (EMT) 是上皮细胞获得间质(如表型)的事件。EMT可作为一种生理现象发生在组织发展和伤口愈合中,但最重要的是,EMT可为上皮癌细胞赋予高度侵袭性。E-钙黏蛋白(一种重要的细胞-细胞粘附蛋白)表达的减少,连同间质标记(如N-钙黏蛋白、波形蛋白、纤连蛋白)表达的增加,一起表征EMT进程,并通常与肿瘤迁移和远端转移有关。广阔的微环境和细胞内因子调节肿瘤发展进程。粘附相关蛋白(如E-钙黏蛋白)和EMT相关转录因子之间的动态相互关系,以及对TWIST的特别关注,将在本文中被讨论,旨在找到合适的生物通路作为癌症治疗的潜在靶标。如PI3K/AKT/TWIST通路在调节E-钙黏蛋白表达中的作用等新兴概念将被强调,因其似乎一直参与细胞EMT。作为沉默特定蛋白表达工具的RNA干扰的著名有效性已成为控制不同肿瘤亚群的策略焦点。尽管寡核苷酸巨大的敏感性和体内稳定性低,新 (nano) 技术有望使RNAi应用于临床癌症治疗。
关键词: 上皮间质转分化 (EMT),E-钙黏蛋白,远端转移,PI3K/AKT2/TWIST,RNA干扰 (RNAi)。
Current Gene Therapy
Title:EMT Blockage Strategies: Targeting Akt Dependent Mechanisms for Breast Cancer Metastatic Behaviour Modulation
Volume: 15 Issue: 3
Author(s): D. Rafael, S. Doktorovova, H.F. Florindo, P. Gener, I. Abasolo, S.Jr. Schwartz and M.A. Videira
Affiliation:
关键词: 上皮间质转分化 (EMT),E-钙黏蛋白,远端转移,PI3K/AKT2/TWIST,RNA干扰 (RNAi)。
摘要: Epithelial Mesenchymal Transition (EMT) is an event where epithelial cells acquire mesenchymal- like phenotype. EMT can occur as a physiological phenomenon during tissue development and wound healing, but most importantly, EMT can confer highly invasive properties to epithelial carcinoma cells. The impairment of E-cadherin expression, an essential cell-cell adhesion protein, together with an increase in the expression of mesenchymal markers, such as N-cadherin, vimentin, and fibronectin, characterize the EMT process and are usually correlated with tumor migration, and metastization. A wide range of micro-environmental and intracellular factors regulate tumor development and progression. The dynamic cross-talk between the adhesion-related proteins such as E-cadherin and the EMT-related transcription factors, with special focus on TWIST, will be discussed here, with the aim of finding a suitable biological pathway to be used as potential target for cancer therapy. Emerging concepts such as the role of the PI3K/AKT/TWIST pathway in the regulation of the E-cadherin expression will be highlighted, since it seems to be consistently involved in cells EMT. The wellknown efficacy of the RNA interference as a tool to silence the expression of specific proteins has come into focus as a strategy to control different tumor sub-populations. Despite the oligonucleotides enormous sensitivity and low in vivo stability, new (nano)technological solutions are expected to enable RNAi clinical application in cancer therapy.
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D. Rafael, S. Doktorovova, H.F. Florindo, P. Gener, I. Abasolo, S.Jr. Schwartz and M.A. Videira , EMT Blockage Strategies: Targeting Akt Dependent Mechanisms for Breast Cancer Metastatic Behaviour Modulation, Current Gene Therapy 2015; 15 (3) . https://dx.doi.org/10.2174/1566523215666150126123642
DOI https://dx.doi.org/10.2174/1566523215666150126123642 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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