Nudt2编码催化Ap4A水解的二腺苷四磷酸(Ap4A)水解酶,并参与赖氨酰tRNA合成酶-Ap4A-Nudt2(LysRS-Ap4A-Nudt2)信号通路。我们先前已经证明该途径在非小细胞肺癌中是活跃的。Nudt2被证明与乳腺癌的细胞增殖有关,使其成为癌症治疗的重要靶点。目前,Nudt2在恶性黑色素瘤中的功能尚未得到证实。因此,我们研究了Nudt2在人类黑色素瘤生长中所起的作用.我们的研究表明,Nudt2敲低在体外抑制了人黑色素瘤细胞的锚定非依赖性生长。通过研究Nudt2敲低对小鼠异种移植模型中细胞形成肿瘤的能力所起的作用来确定Nudt2的体内作用。在该模型中,Nudt2敲低显著抑制肿瘤生长。此外,Nudt2的过表达导致这些细胞的非贴壁生长增加,而Nudt2敲除减少了它们的迁移。此外,Nudt2敲低降低波形蛋白表达。波形蛋白是参与上皮间质转化(EMT)过程的间质标志物之一。因此,Nudt2在促进黑色素瘤的锚定非依赖性生长和细胞迁移中起重要作用。
Nudt2 encodes a diadenosine tetraphosphate (Ap4A) hydrolase that catalyzes the hydrolysis of Ap4A and is involved in the lysyl tRNA synthetase-Ap4A-
Nudt2 (LysRS-Ap4A-
Nudt2) signaling pathway. We have previously demonstrated that this pathway is active in non-small cell lung cancer. Nudt2 was shown to be involved in cell proliferation in breast cancer, making it an important target in cancer therapy. Currently, the function of Nudt2 in malignant melanoma has not been demonstrated. Therefore, we investigated the role played by Nudt2 in the growth of human melanoma. Our study showed that Nudt2 knockdown suppressed anchorage-independent growth of human melanoma cells in vitro. The in vivo effect of
Nudt2 was determined by investigating the role played by
Nudt2 knockdown on the ability of the cells to form tumors in a mice xenograft model.
Nudt2 knockdown significantly suppressed tumor growth in this model. Moreover, overexpression of Nudt2 resulted in an increase in anchorage-independent growth of these cells, whereas
Nudt2 knockdown decreased their migration. In addition,
Nudt2 knockdown reduced vimentin expression. Vimentin is one of the mesenchymal markers that are involved in the epithelial mesenchymal transition (EMT) process. Thus, Nudt2 plays an important role in promoting anchorage-independent growth and cell migration in melanoma.