Signaling pathways and mesenchymal transition in pediatric high-grade glioma.
Signaling pathways and mesenchymal transition in pediatric high-grade glioma.
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DOI：
10.1007/s00018-017-2714-7
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Hulleman E
中科院分区：
文献类型：
--
作者：
Meel MH;Schaper SA;Kaspers GJL;Hulleman E
小儿高级胶质瘤（pHGG），包括弥漫性内在脑桥胶质瘤（DIPG），是儿童中最致命的癌症类型。近年来，很明显，这些肿瘤是由表观遗传事件驱动的，主要是涉及编码组蛋白3基因的突变，使它们与成人肿瘤不同。这些肿瘤对化疗特别有抵抗力，对放疗只有暂时的反应。此外，其微妙的位置和弥漫性生长模式使得完全手术切除是不可能的。在许多其他形式的癌症中，化疗和放射耐药与弥漫性侵袭性表型相结合，与称为上皮-间质转化（EMT）的转录程序有关。这个程序的激活允许癌细胞单独存活，侵入周围组织并转移。它还使他们能够在暴露于细胞毒性治疗中生存，包括化疗药物和放疗。我们认为EMT在pHGG和DIPG的生物学和治疗耐药性中起着重要的作用，但人们对其知之甚少。本文综述了目前对癌症中上皮细胞向间质细胞转化的主要信号转导途径和转录因子的了解，特别是儿童HGG和DIPG。尽管pHGG和DIPG的间质转化尚未被专门研究，但已经描述了参与EMT的途径激活和高水平的转录因子。我们得出结论，间质转化可能是pHGG和DIPG生物学的一个重要因素，值得进一步研究以开发新的治疗方法。
Pediatric high-grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPG), are the most lethal types of cancer in children. In recent years, it has become evident that these tumors are driven by epigenetic events, mainly mutations involving genes encoding Histone 3, setting them apart from their adult counterparts. These tumors are exceptionally resistant to chemotherapy and respond only temporarily to radiotherapy. Moreover, their delicate location and diffuse growth pattern make complete surgical resection impossible. In many other forms of cancer, chemo- and radioresistance, in combination with a diffuse, invasive phenotype, are associated with a transcriptional program termed the epithelial-to-mesenchymal transition (EMT). Activation of this program allows cancer cells to survive individually, invade surrounding tissues and metastasize. It also enables them to survive exposure to cytotoxic therapy, including chemotherapeutic drugs and radiation. We here suggest that EMT plays an important, yet poorly understood role in the biology and therapy resistance of pHGG and DIPG. This review summarizes the current knowledge on the major signal transduction pathways and transcription factors involved in the epithelial-to-mesenchymal transition in cancer in general and in pediatric HGG and DIPG in particular. Despite the fact that the mesenchymal transition has not yet been specifically studied in pHGG and DIPG, activation of pathways and high levels of transcription factors involved in EMT have been described. We conclude that the mesenchymal transition is likely to be an important element of the biology of pHGG and DIPG and warrants further investigation for the development of novel therapeutics.
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