Cited by 239Telomeres, Telomerase, and SenescenceCancer-related Molecular PathwaysGenetics, Aging, and Longevity in Model Organisms

A Senescence-Inflammatory Switch from Cancer-Inhibitory to Cancer-Promoting Mechanism

Open access
Pribluda, Ariel, Elyada, Ela, Wiener, Zoltan, Hamza, Haya, Goldstein, Robert E., Biton, Moshe, Burstain, Ido, Morgenstern, Yael +12 more·2013·Cancer Cell

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.

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Registry

Crossref · 10.1016/j.ccr.2013.06.005

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  • Even in the same tissue, the same triggers can either suppress tumorigenesis by inducing senescence or promote tumorigenesis, as in cytokine-induced senescence.

    “Even in the same tissue, the same triggers can either suppress (by inducing senescence) or promote tumorigenesis, as in the case for cytokine-induced senescence 128,143”

    From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [143]

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Authors
Pribluda, A., Elyada, E., Wiener, Z., Hamza, H., Goldstein, R. E., Biton, M., Burstain, I., Morgenstern, Y., Brachya, G., Billauer, H., Biton, S., Snir-Alkalay, I., Vucic, D., Schlereth, K., Mernberger, M., Stiewe, T., Oren, M., Alitalo, K., Pikarsky, E., & Ben-Neriah, Y.
Affiliations
  • Hebrew University of Jerusalem (IL)
  • Genentech (US)
  • Philipps University of Marburg (DE)
  • Weizmann Institute of Science (IL)
  • University of Helsinki (FI)
Corresponding author
Pikarsky, Eli
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2013-08
Volume
24
Issue
2
Pages
242-256
ISSN
1535-6108 (ISSN-L)
OpenAlex
W1981033124
Cited by
239
References
56
Citations by year
2026: 8 · 2025: 17 · 2024: 22 · 2023: 20 · 2022: 20 · 2021: 20 · 2020: 13 · 2019: 20 · 2018: 18 · 2017: 26 · 2016: 23 · 2015: 15 · 2014: 14 · 2013: 3
FWCI
12.69
Type
journal article
Language
en
Update notices
erratum (2015-06-08)
Open access
Locations
  • Cancer Cell (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
cellular senescence, p53, CSNK1A1, colorectal cancer, intestinal organoids, carcinogenesis, tumor invasion, nonsteroidal anti-inflammatory drugs, anti-inflammatory therapy
MeSH terms
Animals, Anti-Inflammatory Agents, Non-Steroidal, Cell Transformation, Neoplastic, Inflammation, Neoplasms, Cellular Senescence, Mice, Knockout, Mice

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