Universität zu Köln

Kim, Chun ORCID: 0000-0001-9497-708X and Pasparakis, Manolis ORCID: 0000-0002-9870-0966 (2014). Epidermal p65/NF-kappa B signalling is essential for skin carcinogenesis. EMBO Mol. Med., 6 (7). S. 970 - 984. HOBOKEN: WILEY. ISSN 1757-4684

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Abstract

The nuclear factor kappa B (NF-kappa B) signalling pathway exhibits both tumour-promoting and tumour-suppressing functions in different tissues and models of carcinogenesis. In particular in epidermal keratinocytes, NF-kappa B 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-kappa B 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kim, Chun UNSPECIFIED orcid.org/0000-0001-9497-708X UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-434476
DOI:	10.15252/emmm.201303541
Journal or Publication Title:	EMBO Mol. Med.
Volume:	6
Number:	7
Page Range:	S. 970 - 984
Date:	2014
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1757-4684
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; SQUAMOUS-CELL CARCINOMAS; NECROSIS-FACTOR-ALPHA; DNA-DAMAGE; MOUSE MODEL; CANCER DEVELOPMENT; TRANSGENIC MICE; ACTIVATION; PROLIFERATION; KERATINOCYTES Multiple languages Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/43447