Abstract:
:Snail1 is a master regulator of the epithelial-mesenchymal transition (EMT) and has been implicated in key tumor biological processes such as invasion and metastasis. It has been previously shown that poly(ADP-ribose) polymerase-1 (PARP-1) knockdown, but not PARP inhibition, downregulates the expression of Snail1. In this study we have characterized a novel regulatory mechanism controlling Snail1 protein expression through poly(ADP-ribosyl)ation. The effect is not only limited to repression of Snail1 transcription but also to downregulated Snail1 protein stability. PARP-1 (but not PARP-2) poly(ADP) ribosylates Snail1, both in vivo and in vitro, and interacts with Snail1, an association that is sensitive to PARP inhibitors. PARP inhibition has also clear effects on EMT phenotype of different tumor cells, including Snail1 downregulation, E-cadherin upregulation, decreased cell elongation and invasiveness. Therefore, this study reveals a new regulatory mechanism of Snail1 activation through poly(ADP-ribosyl)ation with consequences in malignant transformation through EMT.
journal_name
Oncogenejournal_title
Oncogeneauthors
Rodríguez MI,González-Flores A,Dantzer F,Collard J,de Herreros AG,Oliver FJdoi
10.1038/onc.2011.153subject
Has Abstractpub_date
2011-10-20 00:00:00pages
4365-72issue
42eissn
0950-9232issn
1476-5594pii
onc2011153journal_volume
30pub_type
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