ArticleAging cell2008
p16INK4a-induced senescence is disabled by melanoma-associated mutations.
Article in Aging cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 61 citations in OpenAlex.
- Improving diagnostic accuracy in atypical melanocytic tumors using p16 immunohistochemistry and 9p21 fluorescence in situ hybridization: analysis of 206 second opinion cases.Scientific reports · 2025Article
- Whole-exome sequencing identifies distinct genomic aberrations in eccrine porocarcinomas and poromas.Orphanet journal of rare diseases · 2025Article
- Alpha-synuclein knockout impairs melanoma development and alters DNA damage repair in the TG3 mouse model in a sex-dependent manner.Frontiers in oncology · 2025Article
- Loss of p14 diminishes immunogenicity in melanoma via non-canonical Wnt signaling by reducing the peptide surface density.Molecular oncology · 2024Article
- P16INK4A-More Than a Senescence Marker.Life (Basel, Switzerland) · 2022Review
- Anagliptin prevented interleukin 1β (IL-1β)-induced cellular senescence in vascular smooth muscle cells through increasing the expression of sirtuin1 (SIRT1).Bioengineered · 2021Article
- Loss of p16: A Bouncer of the Immunological Surveillance?Life (Basel, Switzerland) · 2021Review
- Article
- Genetic Alterations in the INK4a/ARF Locus: Effects on Melanoma Development and Progression.Biomolecules · 2020Review
- A cmap-enabled gene expression signature-matching approach identifies small-molecule inducers of accelerated cell senescence.BMC genomics · 2019Article
- p16: cycling off the beaten path.Molecular & cellular oncology · 2019Article
- Review
- The Strange Case of CDK4/6 Inhibitors: Mechanisms, Resistance, and Combination Strategies.Trends in cancer · 2017Review
- Senescence-Like Phenotypes in Human Nevi.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells.Pigment cell & melanoma research · 2015Article
- Molecular pathology of cutaneous melanoma.Melanoma management · 2014Review
- Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells.Chemistry Central journal · 2012Article
- Article
- A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells.Cancer cell · 2011Article
- The evolving role of radiation therapy in the management of malignant melanoma.International journal of radiation oncology, biology, physics · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p16(INK4a)-Rb tumour suppressor pathway is required for the initiation and maintenance of cellular senescence, a state of permanent growth arrest that acts as a natural barrier against cancer progression. Senescence can be overcome if the pathway is not fully engaged, and this may occur when p16(INK4a) is inactivated. p16(INK4a) is frequently altered in human cancer and germline mutations affecting p16(INK4a) have been linked to melanoma susceptibility. To characterize the functions of melanoma-associated p16(INK4a) mutations, in terms of promoting proliferative arrest and initiating senescence, we utilized an inducible expression system in a melanoma cell model. We show that wild-type p16(INK4a) promotes rapid cell cycle arrest that leads to a senescence programme characterized by the appearance of chromatin foci, activation of acidic beta-galactosidase activity, p53 independence and Rb dependence. Accumulation of wild-type p16(INK4a) also promoted cell enlargement and extensive vacuolization independent of Rb status. In contrast, the highly penetrant p16(INK4a) variants, R24P and A36P failed to arrest cell proliferation and did not initiate senescence. We also show that overexpression of CDK4, or its homologue CDK6, but not the downstream kinase, CDK2, inhibited the ability of wild-type p16(INK4a) to promote cell cycle arrest and senescence. Our data provide the first evidence that p16(INK4a) can initiate a CDK4/6-dependent autonomous senescence programme that is disabled by inherited melanoma-associated mutations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.