NDPKA 不仅是一种转移抑制因子——要意识到它在神经母细胞瘤中具有促进转移的作用。

NDPKA is not just a metastasis suppressor - be aware of its metastasis-promoting role in neuroblastoma.

机构信息

Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

Lab Invest. 2018 Feb;98(2):219-227. doi: 10.1038/labinvest.2017.105. Epub 2017 Oct 9.

Abstract

NDPK-A, encoded by nm23-H1 (also known as NME1) was the first metastasis suppressor discovered. Much of the attention has been focused on the metastasis-suppressing role of NDPK-A in human tumors, including breast carcinoma and melanoma. However, compelling evidence points to a metastasis-promoting role of NDPK-A in certain tumors such as neuroblastoma and lymphoma. To balance attention on this contrariety of NDPK-A in different cancer types, this review addresses the metastasis-promoting role of NDPK-A in neuroblastoma. Neuroblastoma is an embryonic tumor, arising from neural crest cells that fail to differentiate into the sympathetic nervous system. We summarize and discuss nm23-H1 genetics and the prognosis of neuroblastoma, structural and functional changes associated with the S120G mutation of NDPK-A, as well as the evidence supporting the role of NDPK-A as a metastasis promoter. Also discussed are the NDPK-A relevant molecular determinants of neuroblastoma metastasis, and metastasis-relevant neural crest development. Because of NDPK-A's dichotomous role in tumor metastasis as both a suppressor and a promoter, tumor genome/exome profiles are necessary to identify the molecular drivers of metastasis in the NDPK-A network for developing tumor-specific therapies.

摘要

NDPK-A 由 nm23-H1(也称为 NME1)编码,是第一个被发现的转移抑制因子。人们对 NDPK-A 在人类肿瘤(包括乳腺癌和黑色素瘤)中的转移抑制作用给予了大量关注。然而,有确凿的证据表明 NDPK-A 在某些肿瘤(如神经母细胞瘤和淋巴瘤)中具有促进转移的作用。为了平衡 NDPK-A 在不同癌症类型中的这种相反作用,本综述探讨了 NDPK-A 在神经母细胞瘤中的促转移作用。神经母细胞瘤是一种胚胎肿瘤,起源于未能分化为交感神经系统的神经嵴细胞。我们总结和讨论了 nm23-H1 遗传学和神经母细胞瘤的预后、与 NDPK-A 的 S120G 突变相关的结构和功能变化,以及支持 NDPK-A 作为转移促进因子的证据。还讨论了与神经母细胞瘤转移相关的 NDPK-A 相关分子决定因素,以及与转移相关的神经嵴发育。由于 NDPK-A 在肿瘤转移中具有双重作用,既是抑制因子又是促进因子,因此需要肿瘤基因组/外显子谱来识别 NDPK-A 网络中转移的分子驱动因素,以开发针对肿瘤的特异性治疗方法。

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