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Cancer Cell. 2013 Aug 12;24(2):242-56. doi: 10.1016/j.ccr.2013.06.005. Epub 2013 Jul 25.

A senescence-inflammatory switch from cancer-inhibitory to cancer-promoting mechanism.

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1
The Lautenberg Center for Immunology, Institute of Medical Research, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

Erratum in

  • Cancer Cell. 2015 Jun 8;27(6):877-8.

Abstract

Senescence, perceived as a cancer barrier, is paradoxically associated with inflammation, which promotes tumorigenesis. Here, we characterize a distinct low-grade inflammatory process in stressed epithelium that is related to para-inflammation; this process either represses or promotes tumorigenesis, depending on p53 activity. Csnk1a1 (CKIα) downregulation induces a senescence-associated inflammatory response (SIR) with growth arrest in colorectal tumors, which loses its growth control capacity in the absence of p53 and instead, accelerates growth and invasiveness. Corresponding processes occur in CKIα-deleted intestinal organoids, assuming tumorigenic transformation properties ex vivo, upon p53 loss. Treatment of organoids and mice with anti-inflammatory agents suppresses the SIR and prevents p53-deficient organoid transformation and mouse carcinogenesis. SIR/para-inflammation suppression may therefore constitute a key mechanism in the anticarcinogenic effects of nonsteroidal anti-inflammatory drugs.

Comment in

PMID:
23890787
DOI:
10.1016/j.ccr.2013.06.005
[Indexed for MEDLINE]
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