Potential therapeutic targets of epithelial-mesenchymal transition in melanoma.
Potential therapeutic targets of epithelial-mesenchymal transition in melanoma.
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DOI：
10.1016/j.canlet.2017.01.029
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发表时间：
2017-04-10
期刊：
影响因子：
9.7
通讯作者：
Afaq F
中科院分区：
文献类型：
--
作者：
Pearlman RL;Montes de Oca MK;Pal HC;Afaq F
黑色素瘤是一种黑色素细胞的皮肤肿瘤生长，具有很大的侵袭和转移潜力，特别是在没有早期有效治疗的情况下。上皮-间质转化（EMT）是黑素细胞失去其上皮特征并获得间质表型的过程。间充质蛋白表达增加黑色素瘤的运动性、侵袭性和转移潜能许多途径在促进间充质蛋白表达中起作用，包括RAS/RAF/MEK/ERK、PI 3 K/AKT/mTOR、Wnt/β-连环蛋白等。这些途径的下游效应物诱导EMT转录因子的表达，包括Snail、Slug、Twist和Zeb，其促进上皮细胞的抑制和间充质特征的诱导。新兴研究表明，各种小分子抑制剂以及植物化学物质可以影响EMT的进展，甚至可能逆转这一过程，诱导上皮标志物的重新表达。植物化学物质作为补充处理选择特别令人感兴趣，因为它们的毒性相对较低，具有抗EMT特性。使用合成小分子和植物化学物质调节EMT信号通路是减少转移性黑色素瘤侵袭性进展的潜在治疗策略。在这篇综述中，我们讨论了新兴的途径和转录因子的目标，调节EMT和评估潜在的合成小分子和天然存在的化合物，可能会减少转移性黑色素瘤的进展。
Melanoma is a cutaneous neoplastic growth of melanocytes with great potential to invade and metastasize, especially when not treated early and effectively. Epithelial-mesenchymal transition (EMT) is the process by which melanocytes lose their epithelial characteristics and acquire mesenchymal phenotypes. Mesenchymal protein expression increases the motility, invasiveness, and metastatic potential of melanoma. Many pathways play a role in promotion of mesenchymal protein expression including RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, Wnt/β-catenin, and several others. Downstream effectors of these pathways induce expression of EMT transcription factors including Snail, Slug, Twist, and Zeb that promote repression of epithelial and induction of mesenchymal character. Emerging research has demonstrated that a variety of small molecule inhibitors as well as phytochemicals can influence the progression of EMT and may even reverse the process, inducing re-expression of epithelial markers. Phytochemicals are of particular interest as supplementary treatment options because of their relatively low toxicities and anti-EMT properties. Modulation of EMT signaling pathways using synthetic small molecules and phytochemicals is a potential therapeutic strategy for reducing the aggressive progression of metastatic melanoma. In this review, we discuss the emerging pathways and transcription factor targets that regulate EMT and evaluate potential synthetic small molecules and naturally occurring compounds that may reduce metastatic melanoma progression.