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A Senescence-Inflammatory Switch from Cancer-Inhibitory to Cancer-Promoting Mechanism
Open accessAbstract
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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“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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Metadata
- 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
- ORCID
- 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
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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