The Epithelial-to-Mesenchymal Transition-Like Process in Glioblastoma: An Updated Systematic Review and In Silico Investigation
The Epithelial-to-Mesenchymal Transition-Like Process in Glioblastoma: An Updated Systematic Review and In Silico Investigation
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DOI：
10.1002/med.21408
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发表时间：
2017-03-01
影响因子：
13.3
通讯作者：
Wink, Marcia R.
中科院分区：
文献类型：
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作者：
Iser, Isabele C.;Pereira, Mariana B.;Wink, Marcia R.
多形性胶质母细胞瘤（GBM）是最具侵袭性的脑癌形式，因为其高度侵袭性的性质阻碍了所有肿瘤细胞的手术切除，使复发不可避免。然而，胶质瘤细胞侵入周围组织的机制仍不清楚。在这种情况下，上皮-间充质转化（EMT）已成为这种侵袭性状态的关键调节因子，尽管该程序在恶性胶质瘤中的真实的相关性仍有争议，但它与GBM恶性肿瘤密切相关。EMT是一个非常复杂的过程，由几个家族的转录因子通过许多信号通路调节，形成一个网络，允许癌细胞获得侵袭性并穿透邻近的基质，从而形成有利于癌症进展和转移的微环境。本文就EMT的分子机制，包括EMT因子、耐药、miRNA和新的治疗策略等进行综述。此外，我们解决了有争议的问题，间充质转移GBM与生物信息学分析表明，在上皮和间充质表型方面，大多数GBM样本分析有更多的配置文件间充质比上皮。如果被诱导，这种表型可以在胶质瘤细胞中的EMT样过程中向甚至更多的间充质表型转变。更好地了解肿瘤扩散过程中EMT的分子调控将有助于在治疗GBM时提供潜在的治疗干预措施。(C)2016 Wiley Periodicals，Inc.
Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer due to its highly invasive nature that impedes the surgical removal of all tumor cells, making relapse inevitable. However, the mechanisms used by glioma cells to invade the surrounding tissue are still unclear. In this context, epithelial-to-mesenchymal transition (EMT) has emerged as a key regulator of this invasive state and although the real relevance of this program in malignant glioma is still controversial, it has been strongly associated with GBM malignancy. EMT is a very complex process regulated by several families of transcriptional factors through many signaling pathways that form a network that allows cancer cells to acquire invasive properties and penetrate the neighboring stroma, resulting in the formation of an advantageous microenvironment for cancer progression and metastasis. In this systematic review, we focus on the molecular mechanisms of EMT including EMT-factors, drug resistance, miRNA, and new therapeutic strategies. In addition, we address controversial questions about mesenchymal shift in GBMs with a bioinformatics analysis to show that in terms of epithelial and mesenchymal phenotype, the majority of GBMs samples analyzed have a profile more mesenchymal than epithelial. If induced, this phenotype can be shifted toward an even more mesenchymal phenotype in an EMT-like process in glioma cells. A better understanding of the molecular regulation of the EMT during tumor spreading will help to provide potential therapeutic interventions to target this program when treating GBM. (C) 2016 Wiley Periodicals, Inc.