NME genes in epithelial morphogenesis.
NME genes in epithelial morphogenesis.
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DOI：
10.1007/s00210-011-0607-0
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发表时间：
2011-10
影响因子：
3.6
通讯作者：
Hsu, Tien
中科院分区：
文献类型：
--
作者：
Hsu, Tien
NME基因家族编码高度保守的多功能蛋白，已被证明参与核酸代谢、能量稳态、细胞信号转导和癌症进展。一些家族成员，特别是异构体1和2，由于其潜在的抗转移活性而引起了广泛的兴趣。遗憾的是，由于这些蛋白质具有众多的分子功能，包括核苷二磷酸激酶、蛋白激酶、核酸酶、转录因子、生长因子等，因此对这一关键功能的机制解释很少。此外，不同的研究表明，在临床样本中，NME表达水平与肿瘤进展之间存在相互矛盾的预后相关性。因此，使用柔韧的体内系统进行分析，对于解开这一基因家族复杂功能的至少某些方面变得至关重要。最近利用果蝇遗传系统的研究表明，NME在调节上皮细胞的运动和形态发生方面发挥了作用，这一点在哺乳动物上皮细胞培养中也得到了证实。这一功能是通过促进运动上皮细胞中生长因子受体的内化，以及形成组织衬里的上皮细胞中的黏附连接成分，如E-钙粘附素和β-连环蛋白来介导的。有趣的是，上皮细胞中的NME基因似乎在一定的表达水平范围内发挥作用。下调或过度表达都会扰乱上皮细胞的完整性，导致不同方面的上皮细胞异常。这种双相功能为已有文献记载的抗转移活性和可疑的致癌功能提供了可信的解释。这篇综述总结了这些最新的发现，并讨论了它们的含义。
The NME family of genes encodes highly conserved multifunctional proteins that have been shown to participate in nucleic acid metabolism, energy homeostasis, cell signaling, and cancer progression. Some family members, particularly isoforms 1 and 2, have attracted extensive interests because of their potential anti-metastasis activity. Unfortunately, there have been few consensus mechanistic explanations for this critical function because of the numerous molecular functions ascribed to these proteins, including nucleoside diphosphate kinase, protein kinase, nuclease, transcription factor, growth factor, among others. In addition, different studies showed contradictory prognostic correlations between NME expression levels and tumor progression in clinical samples. Thus, analyses using pliable in vivo systems have become critical for unraveling at least some aspects of the complex functions of this family of genes. Recent works using the Drosophila genetic system have suggested a role for NME in regulating epithelial cell motility and morphogenesis, which has also been demonstrated in mammalian epithelial cell culture. This function is mediated by promoting internalization of growth factor receptors in motile epithelial cells, and the adherens junction components such as E-cadherin and β-catenin in epithelia that form the tissue linings. Interestingly, NME genes in epithelial cells appear to function in a defined range of expression levels. Either down-regulation or over-expression can perturb epithelial integrity, resulting in different aspects of epithelial abnormality. Such biphasic functions provide a plausible explanation for the documented anti-metastatic activity and the suspected oncogenic function. This review summarizes these recent findings and discusses their implications.
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影响因子：
2.7
作者：
DEAROLF, CR;HERSPERGER, E;SHEARN, A
通讯作者：
SHEARN, A
DOI：
10.1111/j.1432-1033.1995.200_c.x
发表时间：
1995-11-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
ENGEL, M;VERON, M;WELTER, C
通讯作者：
WELTER, C
影响因子：
2.4
作者：
FAN, CL;HALL, LM;BROWN, GM
通讯作者：
BROWN, GM
影响因子：
4.8
作者：
Cuello, F;Schulze, RA;Wieland, T
通讯作者：
Wieland, T
影响因子：
64.5
作者：
BIGGS, J;HERSPERGER, E;SHEARN, A
通讯作者：
SHEARN, A