Women's Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Naunyn Schmiedebergs Arch Pharmacol. 2011 Oct;384(4-5):351-62. doi: 10.1007/s00210-011-0646-6. Epub 2011 Jun 29.
Nm23-H1, also known as NDPK-A, was the first of a class of metastasis suppressor genes to be identified. Overexpression of Nm23-H1 in metastatic cell lines (melanoma, breast carcinoma, prostate, colon, hepatocellular, and oral squamous cell carcinoma) reduced cell motility in in vitro assays and metastatic potential in xenograft models, without a significant effect on primary tumor size. The mechanism of Nm23-H1 suppression of metastasis, however, is incompletely understood. Nm23-H1 has been reported to bind proteins, including those in small G-protein complexes, transcriptional complexes, the Map kinase, the TGF-β signaling pathways and the cytoskeleton. Evidence supporting these associations is presented together with evidence of resultant biochemical and phenotypic consequences of association. Cumulatively, the data suggest that part of the anti-metastatic function of Nm23-H1 lies in pathways that it interrupts via binding and inactivation of proteins.
Nm23-H1，也称为 NDPK-A，是首批被鉴定出的转移抑制基因之一。在转移性细胞系（黑色素瘤、乳腺癌、前列腺癌、结肠癌、肝癌和口腔鳞状细胞癌）中过表达 Nm23-H1，可降低体外检测中的细胞迁移能力和异种移植模型中的转移潜能，而对原发性肿瘤大小没有显著影响。然而，Nm23-H1 抑制转移的机制尚不完全清楚。据报道，Nm23-H1 可与多种蛋白质结合，包括小 G 蛋白复合物、转录复合物、Map 激酶、TGF-β 信号通路和细胞骨架中的蛋白质。本文提出了支持这些关联的证据，以及关联导致的生化和表型后果的证据。综合来看，这些数据表明，Nm23-H1 的部分抗转移功能在于通过与蛋白质结合和失活来阻断信号通路。
