Cited by 102Telomeres, Telomerase, and SenescenceCancer-related Molecular PathwaysGenetics, Aging, and Longevity in Model Organisms

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WNT16B Is a New Marker of Cellular Senescence That Regulates p53 Activity and the Phosphoinositide 3-Kinase/AKT Pathway

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Binet, Romuald, Ythier, Damien, Robles, Ana I., Collado, Manuel, Larrieu, Delphine, Fonti, Claire, Brambilla, Elisabeth, Brambilla, Christian, Serrano, Manuel, Harris, Curtis C., Pedeux, Rémy·2009·Cancer Research

DOI 10.1158/0008-5472.can-09-1016PMC PMC7439003

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Abstract

Senescence is a tumor suppression mechanism that is induced by several stimuli, including oncogenic signaling and telomere shortening, and controlled by the p53/p21WAF1 signaling pathway. Recently, a critical role for secreted factors has emerged, suggesting that extracellular signals are necessary for the onset and maintenance of senescence. Conversely, factors secreted by senescent cells may promote tumor growth. By using expression profiling techniques, we searched for secreted factors that were overexpressed in fibroblasts undergoing replicative senescence. We identified WNT16B, a member of the WNT family of secreted proteins. We found that WNT16B is overexpressed in cells undergoing stress-induced premature senescence and oncogene-induced senescence in both MRC5 cell line and the in vivo murine model of K-RasV12–induced senescence. By small interfering RNA experiments, we observed that both p53 and WNT16B are necessary for the onset of replicative senescence. WNT16B expression is required for the full transcriptional activation of p21WAF1. Moreover, WNT16B regulates activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Overall, we identified WNT16B as a new marker of senescence that regulates p53 activity and the PI3K/AKT pathway and is necessary for the onset of replicative senescence. [Cancer Res 2009;69(24):9183–91]

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Authors: Binet, R., Ythier, D., Robles, A. I., Collado, M., Larrieu, D., Fonti, C., Brambilla, E., Brambilla, C., Serrano, M., Harris, C. C., & Pedeux, R.
Affiliations: Inserm (FR)
Corresponding author: Pedeux, Rémy
ORCID: Binet, Romuald
Robles, Ana I.
Collado, Manuel
Larrieu, Delphine
Brambilla, Elisabeth
Serrano, Manuel
Harris, Curtis C.
Pedeux, Rémy
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2009-12-14
Volume: 69
Issue: 24
Pages: 9183-9191
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-09-1016
PMC: PMC7439003
OpenAlex: W2123104757
Cited by: 101
References: 43
Citations by year: 2026: 1 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 9 · 2015: 9 · 2014: 10 · 2013: 8 · 2012: 6
FWCI: 5.10
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Cancer Institute (Z01BC005794)
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, replicative senescence, stress-induced premature senescence, oncogene-induced senescence, p53, p21, PI3K/Akt signaling, secreted factors, fibroblasts, tumor suppression, senescence-associated secretory phenotype
MeSH terms: Phosphoinositide-3 Kinase Inhibitors, Chromones, Enzyme Inhibitors, Fibroblasts, Humans, Morpholines, Transcription, Genetic, Transfection, Tumor Suppressor Protein p53, Cellular Senescence, Phosphatidylinositol 3-Kinases, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, RNA, Small Interfering, Cyclin-Dependent Kinase Inhibitor p21, Proto-Oncogene Proteins c-akt, Wnt Proteins

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WNT16B Is a New Marker of Cellular Senescence That Regulates p53 Activity and the Phosphoinositide 3-Kinase/AKT Pathway

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