Epidermal p65/ <scp>NF</scp> ‐κB signalling is essential for skin carcinogenesis
In: EMBO Molecular Medicine, Jg. 6 (2014-06-21), S. 970-983
Online
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Zugriff:
The nuclear factor kappa B (NF-κB) signalling pathway exhibits both tumour-promoting and tumour-suppressing functions in different tissues and models of carcinogenesis. In particular in epidermal keratinocytes, NF-κB signalling was reported to exert primarily growth inhibitory and tumour-suppressing functions. Here, we show that mice with keratinocyte-restricted p65/RelA deficiency were resistant to 7, 12-dimethylbenz(a)anthracene (DMBA)-/12-O-tetra decanoylphorbol-13 acetate (TPA)-induced skin carcinogenesis. p65 deficiency sensitized epidermal keratinocytes to DNA damage-induced death in vivo and in vitro, suggesting that inhibition of p65-dependent prosurvival functions prevented tumour initiation by facilitating the elimination of cells carrying damaged DNA. In addition, lack of p65 strongly inhibited TPA-induced epidermal hyperplasia and skin inflammation by suppressing the expression of proinflammatory cytokines and chemokines by epidermal keratinocytes. Therefore, p65-dependent NF-κB signalling in keratinocytes promotes DMBA-/TPA-induced skin carcinogenesis by protecting keratinocytes from DNA damage-induced death and facilitating the establishment of a tumour-nurturing proinflammatory microenvironment.
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Epidermal p65/ <scp>NF</scp> ‐κB signalling is essential for skin carcinogenesis
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Autor/in / Beteiligte Person: | Pasparakis, Manolis ; Kim, Chun |
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Zeitschrift: | EMBO Molecular Medicine, Jg. 6 (2014-06-21), S. 970-983 |
Veröffentlichung: | EMBO, 2014 |
Medientyp: | unknown |
ISSN: | 1757-4684 (print) ; 1757-4676 (print) |
DOI: | 10.15252/emmm.201303541 |
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