Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
Cancer Cell. 2011 Feb 15;19(2):218-31. doi: 10.1016/j.ccr.2010.11.010. Epub 2011 Feb 3.
N-α-acetyltransferase 10 protein, Naa10p, is an N-acetyltransferase known to be involved in cell cycle control. We found that Naa10p was expressed lower in varieties of malignancies with lymph node metastasis compared with non-lymph node metastasis. Higher Naa10p expression correlates the survival of lung cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells.
N-α-乙酰基转移酶 10 蛋白（Naa10p）是一种已知参与细胞周期调控的 N-乙酰基转移酶。我们发现，与无淋巴结转移的肿瘤相比，具有淋巴结转移的多种恶性肿瘤中 Naa10p 的表达水平较低。较高的 Naa10p 表达与肺癌患者的生存相关。Naa10p 显著抑制迁移、肿瘤生长和转移，而不依赖其酶活性。相反，Naa10p 与 PIX 的 GIT 结合域结合，从而阻止 GIT-PIX-Paxillin 复合物的形成，导致内在的 Cdc42/Rac1 活性降低和细胞迁移减少。在 Naa10 转染的肿瘤细胞中强制表达 PIX 恢复了迁移和转移能力。我们认为，Naa10p 通过破坏癌细胞中的迁移复合物 PIX-GIT-Paxillin 发挥肿瘤转移抑制因子的作用。
