PARP10 suppresses tumor metastasis through regulation of Aurora A activity
| Autor: | Dan Song, Xiaoding Hu, Juanjuan Wang, Yahui Zhao, Lifang You, Wenbo Yu, Jiaxue Wu, Jin Ding, Zhaojie Li, Li Wei, Long Yu, Hexige Saiyin |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Carcinoma Hepatocellular Epithelial-Mesenchymal Transition Biology Metastasis Metastasis Suppression Mice 03 medical and health sciences Cell Movement In vivo Proto-Oncogene Proteins Genetics medicine Animals Humans Epithelial–mesenchymal transition Kinase activity Molecular Biology Aurora Kinase A Regulation of gene expression Liver Neoplasms medicine.disease Gene Expression Regulation Neoplastic 030104 developmental biology Cancer research Female Poly(ADP-ribose) Polymerases Signal transduction Neoplasm Transplantation Intracellular HeLa Cells Signal Transduction |
| Zdroj: | Oncogene. 37:2921-2935 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/s41388-018-0168-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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