http://www.cnr.it/ontology/cnr/individuo/prodotto/ID12937
Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas (Articolo in rivista)
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- Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas (Articolo in rivista) (literal)
- Anno
- 2011-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1073/pnas.1110931108 (literal)
- Alternative label
Botti, Elisabetta; Spallone, Giulia; Moretti, Francesca; Marinari, Barbara; Pinetti, Valentina; Galanti, Sergio; De Meo, Paolo D Onorio; De Nicola, Francesca; Ganci, Federica; Castrignanò, Tiziana; Pesole, Graziano; Chimenti, Sergio; Guerrini, Luisa; Fanciulli, Maurizio; Blandino, Giovanni; Karin, Michael; Costanzo, Antonio (2011)
Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas
in Proceedings of the National Academy of Sciences of the United States of America
(literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Botti, Elisabetta; Spallone, Giulia; Moretti, Francesca; Marinari, Barbara; Pinetti, Valentina; Galanti, Sergio; De Meo, Paolo D Onorio; De Nicola, Francesca; Ganci, Federica; Castrignanò, Tiziana; Pesole, Graziano; Chimenti, Sergio; Guerrini, Luisa; Fanciulli, Maurizio; Blandino, Giovanni; Karin, Michael; Costanzo, Antonio (literal)
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- Universita degli Studi di Roma Tor Vergata; Istituto Nazionale Tumori Regina Elena; Consorzio interuniversitario per le Applicazioni di Supercalcolo Per Universita e Ricerca; Universita degli Studi di Bari; Universita degli Studi di Milano; University of California, San Diego (literal)
- Titolo
- Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas (literal)
- Abstract
- The transcription factor interferon regulatory factor 6 (IRF6) regulates craniofacial development and epidermal proliferation. We recently showed that IRF6 is a component of a regulatory feedback loop that controls the proliferative potential of epidermal cells. IRF6 is transcriptionally activated by p63 and induces its proteasome-mediated down-regulation, thereby limiting keratinocyte proliferative potential. We hypothesized that IRF6 may also be involved in Skin carcinogenesis. Hence, we analyzed IRF6 expression in a large series of squamous cell carcinomas (SCCs) and found a strong down-regulation of IRF6 that correlated with tumor invasive and differentiation status. IRF6 down-regulation in SCC cell lines and primary tumors correlates with methylation on a CpG dinucleotide island located in its promoter region. To identify the molecular mechanisms regulating IRF6 potential tumor suppressive activity, we performed a genome-wide analysis by combining ChIP sequencing for IRF6 binding sites and gene expression profiling in primary human keratinocytes after siRNA-mediated IRF6 depletion. We observed dysregulation of cell cycle-related genes and genes involved in differentiation, cell adhesion, and cell-cell contact. Many of these genes were direct IRF6 targets. We also performed in vitro invasion assays showing that IRF6 down-regulation promotes invasive behavior and that reintroduction of IRF6 into SCC cells strongly inhibits cell growth. These results indicate a function for IRF6 in suppression of tumorigenesis in stratified epithelia. (literal)
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