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首页> 外文期刊>Cell and Tissue Research >Hypoxia and hypoxia-inducible factors in neuroblastoma
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Hypoxia and hypoxia-inducible factors in neuroblastoma

机译：神经母细胞瘤中缺氧和缺氧诱导因子

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摘要

Hypoxia (i.e., low oxygen levels) is a known feature of aggressive tumors. Cells, including tumor cells, respond to conditions of insufficient oxygen by activating a transcriptional program mainly driven by hypoxia-inducible factors (HIF)-1 and HIF-2. Both HIF-1α and HIF-2α expression levels have been shown to correlate to patient outcome in various tumor forms and in neuroblastoma, a solid childhood tumor of the sympathetic nervous system, in particular, HIF-2α marks a subpopulation of immature neural crest-like perivascularly located cells and associates with aggressive disease and distant metastasis. It has for long been recognized that the HIF-α subunits are oxygen-dependently regulated at the post-translational level, via ubiquitination and proteasomal degradation. Evidence of oxygen-independent mechanisms of regulation, transcriptional control of EPAS1/HIF2A and possible cytoplasmic activities of HIF-2α has also emerged during recent years. In this review, we discuss these non-conventional actions of HIF-2α, its putative role as a therapeutic target and the constraints it carries, as well as the importance of HIF-2 activity in a vascularized setting, the so-called pseudo-hypoxic state.
机译：缺氧（即低氧水平）是侵袭性肿瘤的已知特征。细胞，包括肿瘤细胞，通过激活主要由缺氧诱导因子（HIF）-1和HIF-2的转录程序响应氧气不足的条件。已经证明HIF-1α和HIF-2α表达水平都与各种肿瘤形式和神经母细胞瘤的患者结果相关，特别是同情神经系统的纯儿童肿瘤，特别是HIF-2α标志着未成熟神经嵴的亚群 - 像血管内定位的细胞和伴有侵袭性疾病和远处转移的缔合。已经认识到，HIF-α亚基通过泛素化和蛋白酶体降解在翻译后水平处缺氧。近年来，近年来，氧化氧依赖性调节机制的证据，EPAS1 / HIF2A的转录控制以及可能的HIF-2α可能的细胞质活性。在本文中，我们讨论了HIF-2α的这些非传统作用，其推定作用作为治疗目标以及它携带的约束，以及HIF-2在血管化环境中的重要性，所谓的伪 - 缺氧状态。

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