Snail nuclear transport: the gateways regulating epithelial-to-mesenchymal transition?
Snail nuclear transport: the gateways regulating epithelial-to-mesenchymal transition?
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DOI：
10.1016/j.semcancer.2014.06.003
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发表时间：
2014-08
影响因子：
14.5
通讯作者：
Azmi AS
中科院分区：
文献类型：
--
作者：
Muqbil I;Wu J;Aboukameel A;Mohammad RM;Azmi AS
上皮-间质转化（Epithelial-to-mesenchymal transition， EMT）及其逆转过程（reverse process， MET）在器官发育生物学中起着重要作用。这是一个精细的过程，当受到干扰时，会导致病理状况，特别是具有侵袭性和转移性行为的癌症。Snail是一种癌基因，已被证实通过直接抑制上皮形态启动子e -钙粘蛋白而成为EMT的启动子。它可以在细胞核、细胞质中以及最近发现的通过分泌囊泡结构在细胞外发挥作用。长期以来，蜗牛的细胞内转运一直受到核孔复合物的调控。其中一种核分裂蛋白进口蛋白α介导蜗牛的进口，而进口蛋白β /出口蛋白1 （Xpo1）或染色体维持区1 （CRM1）是蜗牛的主要核出口蛋白。一些额外的生物调节剂正在出现，它们通过改变蜗牛的亚细胞定位直接调节蜗牛的稳定性。这些观察结果表明，靶向核转运机制可能是针对癌症EMT过程的治疗干预的重要且尚未探索的途径。与此同时，最近发现了一些破坏核转运的新型药物，并正在探索它们在早期临床环境中的抗癌作用。通过这篇综述，我们提供了蜗牛亚细胞定位的调节机制及其如何影响EMT的见解。我们讨论了如何利用核转运功能通过调节蜗牛信号来控制EMT的策略。
Epithelial-to-mesenchymal transition (EMT) and the reverse process (MET) plays central role in organ developmental biology. It is a fine tuned process that when disturbed leads to pathological conditions especially cancers with aggressive and metastatic behavior. Snail is an oncogene that has been well established to be a promoter of EMT through direct repression of epithelial morphology promoter E-cadherin. It can function in the nucleus, in the cytosol and as discovered recently, extracellularly through secretory vesicular structures. The intracellular transport of snail has for long been shown to be regulated by the nuclear pore complex. One of the Karyopherins, importin alpha, mediates snail import, while importin beta/exportin 1 (Xpo1) or chromosome maintenance region 1 (CRM1) is its major nuclear exporter. A number of additional biological regulators are emerging that directly modulate Snail stability by altering its subcellular localization. These observations indicate that targeting the nuclear transport machinery could be an important and as of yet, unexplored avenue for therapeutic intervention against the EMT processes in cancer. In parallel, a number of novel agents that disrupt nuclear transport have recently been discovered and are being explored for their anti-cancer effects in the early clinical settings. Through this review we provide insights on the mechanisms regulating snail subcellular localization and how this impacts EMT. We discuss strategies on how the nuclear transport function can be harnessed to rein in EMT through modulation of snail signaling.
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影响因子：
11.4
作者：
Etchin, J.;Sun, Q.;Kentsis, A.;Farmer, A.;Zhang, Z. C.;Sanda, T.;Mansour, M. R.;Barcelo, C.;McCauley, D.;Kauffman, M.;Shacham, S.;Christie, A. L.;Kung, A. L.;Rodig, S. J.;Chook, Y. M.;Look, A. T.
通讯作者：
Look, A. T.
影响因子：
29.4
作者：
Azmi AS;Aboukameel A;Bao B;Sarkar FH;Philip PA;Kauffman M;Shacham S;Mohammad RM
通讯作者：
Mohammad RM
影响因子：
--
作者：
Azmi AS;Bollig-Fischer A;Bao B;Park BJ;Lee SH;Yong-Song G;Dyson G;Reddy CK;Sarkar FH;Mohammad RM
通讯作者：
Mohammad RM
影响因子：
4.3
作者：
Fang, Ling;Du, William W.;Yang, Burton B.
通讯作者：
Yang, Burton B.
影响因子：
3
作者：
Azmi, Asfar S.
通讯作者：
Azmi, Asfar S.