Web of Science: 9 citations, Scopus: 9 citations, Google Scholar: citations,
Multifaceted role of TREX2 in the skin defense against UV-induced skin carcinogenesis
Manils, Joan (Universitat de Barcelona. Facultat de Medicina)
Gómez, Diana (Universitat de Barcelona. Facultat de Medicina)
Salla Martret, Mercè (Universitat de Barcelona. Facultat de Medicina)
Fischer, Heinz (Medical University of Vienna (Àustria))
Fye, Jason M. (Wake Forest School of Medicine (Winston-Salem, Estats Units d'Amèrica))
Marzo, Elena (Universitat de Barcelona. Facultat de Medicina)
Marruecos, Laura (Universitat de Barcelona. Facultat de Medicina)
Serrano, Inma (Universitat de Barcelona. Facultat de Medicina)
Salgado, Rocío (Hospital del Mar (Barcelona, Catalunya))
Rodrigo, Juan P. (Instituto Universitario de Oncología del Principado de Asturias (Oviedo))
García Pedrero,Juana M. (Instituto Universitario de Oncología del Principado de Asturias (Oviedo))
Serafin, Anna M. (Parc Científic de Barcelona)
Cañas, Xavier (Parc Científic de Barcelona)
Benito, Carmen (Universitat de Barcelona)
Toll, Agustí (Hospital del Mar (Barcelona, Catalunya))
Forcales, Sònia Vanina (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Perrino, Fred W. (Wake Forest School of Medicine (Winston-Salem, Estats Units d'Amèrica))
Eckhart, Leopold (Medical University of Vienna (Àustria))
Soler, Concepció (Universitat de Barcelona. Facultat de Medicina)

Date: 2015
Abstract: TREX2 is a 3'-DNA exonuclease specifically expressed in keratinocytes. Here, we investigated the relevance and mechanisms of TREX2 in ultraviolet (UV)-induced skin carcinogenesis. TREX2 expression was up-regulated by chronic UV exposure whereas it was de-regulated or lost in human squamous cell carcinomas (SCCs). Moreover, we identified SNPs in the TREX2 gene that were more frequent in patients with head and neck SCCs than in healthy individuals. In mice, TREX2 deficiency led to enhanced susceptibility to UVB-induced skin carcinogenesis which was preceded by aberrant DNA damage removal and degradation as well as reduced inflammation. Specifically, TREX2 loss diminished the up-regulation of IL12 and IFNγ, key cytokines related to DNA repair and antitumor immunity. In UV-treated keratinocytes, TREX2 promoted DNA repair and passage to late apoptotic stages. Notably, TREX2 was recruited to low-density nuclear chromatin and micronuclei, where it interacted with phosphorylated H2AX histone, which is a critical player in both DNA repair and cell death. Altogether, our data provide new insights in the molecular mechanisms of TREX2 activity and establish cell autonomous and non-cell autonomous functions of TREX2 in the UVB-induced skin response.
Note: MICINN/BFU2009-07501
Note: MICINN/BFU2010-1567
Note: NIH/GM069962
Rights: Tots els drets reservats
Language: Anglès
Document: article ; recerca ; publishedVersion
Subject: Pell ; Càncer ; DNA damage ; TREX2 ; UV radiation ; Inflammation ; Skin carcinogenesis
Published in: Oncotarget, Vol. 6 Núm. 26 (2015) , ISSN 1949-2553

DOI: 10.18632/oncotarget.4296
PMID: 26090614

22 p, 15.5 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles

 Record created 2016-07-26, last modified 2020-08-15

   Favorit i Compartir