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Title: Multifaceted role of TREX2 in the skin defense against UV-induced skin carcinogenesis
Author: Manils Pacheco, Joan
Gómez Fernández, Diana Lucía
Salla i Martret, Mercè
Fischer, Heinz
Marzo, Elena
Marruecos, Laura
Serrano, Inma
Salgado, Rocío
Rodrigo, Juan P.
Garcia-Pedrero, Juana M.
Serafin, Anna M.
Cañas, Xavier
Benito González, Carmen
Toll Abelló, Agustí
Forcales Fernàndez, Sonia-Vanina
Perrino, Fred W.
Eckhart, Leopold
Soler Prat, Concepció
Keywords: Càncer de pell
Polimorfisme genètic
Radiació ultraviolada
Skin cancer
Genetic polymorphisms
Ultraviolet radiation
Issue Date: 15-Jun-2015
Publisher: Impact Journals
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: Reproducció del document publicat a:
It is part of: Oncotarget, 2015, vol. 6, num. 26, p. 22375-22396
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ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Centres Científics i Tecnològics de la Universitat de Barcelona (CCiTUB))
Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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