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Abstract：
Neuroblastoma is the most common solid extracranial tumor during childhood; it displays extraordinary heterogeneous clinical courses, from spontaneous regression to poor outcome in high-risk patients due to aggressive growth, metastasizing, and treatment resistance. Therefore, the identification and detailed analysis of promising tumorigenic molecular mechanisms are inevitable. This review highlights the abnormal regulation of NF-κB, Nrf2, and Phox2B as well as their interactions among each other in neuroblastoma. NF-κB and Nrf2 play a key role in antioxidant responses, anti-inflammatory regulation and tumor chemoresistance. Recent studies revealed a regulation of NF-κB by means of the Nrf2/antioxidant response element (ARE) system. On the other hand, Phox2B contributes to the differentiation of immature sympathetic nervous system stem cells: this transcription factor regulates the expression of RET, thereby facilitating cell survival and proliferation. As observed in other tumors, we presume striking interactions between NF-κB, Nrf2, and Phox2B, which might constitute an important crosstalk triangle, whose decompensation may trigger a more aggressive phenotype. Consequently, these transcription factors could be a promising target for novel therapeutic approaches and hence, further investigation on their regulation in neuroblastoma shall be reinforced.
摘要：
神经母细胞瘤是儿童时期最常见的实体颅外肿瘤;它表现出非凡的异质性临床过程，从自发消退到高风险患者由于积极生长而导致的不良结局，转移，和治疗阻力。因此,鉴定和详细分析有前景的致瘤分子机制是不可避免的。本文综述了NF-κB的异常调控,Nrf2和Phox2B以及它们在神经母细胞瘤中的相互作用。NF-κB和Nrf2在抗氧化反应中起关键作用，抗炎调节和肿瘤化疗耐药。最近的研究揭示了通过Nrf2/抗氧化反应元件（ARE）系统调节NF-κB。另一方面,Phox2B有助于未成熟交感神经系统干细胞的分化：该转录因子调节RET的表达，从而促进细胞存活和增殖。正如在其他肿瘤中观察到的那样，我们假设NF-κB之间有惊人的相互作用，Nrf2和Phox2B,这可能构成一个重要的串扰三角形，其失代偿可能引发更具侵略性的表型。因此,这些转录因子可能是新的治疗方法的有希望的靶标，因此，应加强对它们在神经母细胞瘤中的调节的进一步研究。
