PARP10 suppresses tumor metastasis through regulation of Aurora A activity
PARP10 suppresses tumor metastasis through regulation of Aurora A activity
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PARP10 通过调节 Aurora A 活性抑制肿瘤转移
DOI：
10.1038/s41388-018-0168-5
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发表时间：
2018-05-01
期刊：
影响因子：
8
通讯作者：
Wu, Jiaxue
中科院分区：
文献类型：
--
作者：
Zhao, Yahui;Hu, Xiaoding;Wu, Jiaxue
ADP核糖化是由细胞内ADP核糖基转移酶(ARTD或PARP)催化的一种多功能的翻译后修饰，包括多聚ADP核糖化和单ADP核糖化。虽然PAR化已经被研究得最彻底，但目前MAR化的功能在很大程度上还不清楚。在这里，我们提供了证据，PARP10，一个单一的ADP核糖转移酶，通过调节上皮-间充质转化(EMT)显著增加肿瘤细胞的迁移和侵袭，并且PARP10抑制体内的肿瘤转移，这依赖于它的酶活性。在机制上，我们发现PARP10与Aurora A相互作用，并被ADP核糖化，并抑制其激酶活性，从而调节其下游信号转导。此外，PARP10在肝内转移性肝细胞癌组织中的表达水平低于其相应的原发肝癌组织和癌旁非肿瘤组织。综上所述，我们的结果表明，PARP10通过负性调节Aurora A活性而在抑制肿瘤转移中发挥重要作用。
ADP-ribosylation, including poly-ADP-ribosylation (PARylation) and mono-ADP-ribosylation (MARylation), is a multifunctional post-translational modification catalyzed by intracellular ADP-ribosyltransferases (ARTDs or PARPs). Although PARylation has been investigated most thoroughly, the function of MARylation is currently largely undefined. Here, we provide evidences that deficiency of PARP10, a mono-ADP-ribosyltransferase, markedly increased the migration and invasion of tumor cells through regulation of epithelial–mesenchymal transition (EMT), and PARP10 inhibited tumor metastasis in vivo, which was dependent on its enzyme activity. Mechanistically, we found that PARP10 interacted with and mono-ADP-ribosylated Aurora A, and inhibited its kinase activity, thereby regulating its downstream signaling. Moreover, the expression level of PARP10 was downregulated in intrahepatic metastatic hepatocellular carcinoma (HCC) compared with its corresponding primary HCC and adjacent non-tumorous tissues. Taken together, our results indicated that PARP10 has an important role in tumor metastasis suppression via negatively regulation of Aurora A activity.