ArticleThe Journal of biological chemistry2011
Escape from p21-mediated oncogene-induced senescence leads to cell dedifferentiation and dependence on anti-apoptotic Bcl-xL and MCL1 proteins.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
36 citing papers in PubMed, 53 citations in OpenAlex.
- MAPK-driven MYC/p21 axis controls senescence bypass and BCL-XL dependence in vincristine-resistant rhabdomyosarcoma.iScience · 2026Article
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
- The p21 resilience network: a conceptual framework linking senescence to ferroptosis and cuproptosis resistance.NPJ systems biology and applications · 2026Review
- Interrogating the regulatory epigenome of cellular senescence.Cellular and molecular life sciences : CMLS · 2025Review
- Synephrine Inhibits Oxidative Stress and HCell biochemistry and biophysics · 2025Article
- Senolytics: charting a new course or enhancing existing anti-tumor therapies?Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Exploring the potential anti-senescence effects of soybean-derived peptide Soymetide in mice hippocampal neurons via the Wnt/β-catenin pathway.Frontiers in pharmacology · 2025Article
- Article
- Engineering principles for rationally design therapeutic strategies against hepatocellular carcinoma.Frontiers in molecular biosciences · 2024Review
- Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence.International journal of molecular sciences · 2023Review
- Expression of Senescence and Apoptosis Biomarkers in Synchronous Bilateral Breast Cancer: A Case Report.Current oncology (Toronto, Ont.) · 2021Article
- Chemotherapy Induces Senescence-Like Resilient Cells Capable of Initiating AML Recurrence.Cancer discovery · 2021Article
- Chemotherapy-induced senescence, an adaptive mechanism driving resistance and tumor heterogeneity.Cell cycle (Georgetown, Tex.) · 2019Review
- SETD1A protects from senescence through regulation of the mitotic gene expression program.Nature communications · 2019Article
- Regulation of senescence escape by TSP1 and CD47 following chemotherapy treatment.Cell death & disease · 2019Article
- Cellular plasticity and metastasis in breast cancer: a pre- and post-malignant problem.Journal of cancer metastasis and treatment · 2019Article
- Article
- Trabectedin modulates the senescence-associated secretory phenotype and promotes cell death in senescent tumor cells by targeting NF-κB.Oncotarget · 2018Article
- Regulation of senescence escape by the cdk4-EZH2-AP2M1 pathway in response to chemotherapy.Cell death & disease · 2018Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogene-induced senescence (OIS) is a tumor suppressor response that induces permanent cell cycle arrest in response to oncogenic signaling. Through the combined activation of the p53-p21 and p16-Rb suppressor pathways, OIS leads to the transcriptional repression of proliferative genes. Although this protective mechanism has been essentially described in primary cells, we surprisingly observed in this study that the OIS program is conserved in established colorectal cell lines. In response to the RAS oncogene and despite the inactivation of p53 and p16(INK4), HT29 cells enter senescence, up-regulate p21(WAF1), and induce senescence-associated heterochromatin foci formation. The same effect was observed in response to B-RAF(v600E) in LS174T cells. We also observed that p21(WAF1) prevents the expression of the CDC25A and PLK1 genes to induce cell cycle arrest. Using ChIP and luciferase experiments, we have observed that p21(WAF1) binds to the PLK1 promoter to induce its down-regulation during OIS induction. Following 4-5 weeks, several clones were able to resume proliferation and escape this tumor suppressor pathway. Tumor progression was associated with p21(WAF1) down-regulation and CDC25A and PLK1 reexpression. In addition, OIS and p21(WAF1) escape was associated with an increase in DNA damage, an induction of the epithelial-mesenchymal transition program, and an increase in the proportion of cells expressing the CD24(low)/CD44(high) phenotype. Results also indicate that malignant cells having escaped OIS rely on survival pathways induced by Bcl-xL/MCL1 signaling. In light of these observations, it appears that the transcriptional functions of p21(WAF1) are active during OIS and that the inactivation of this protein is associated with cell dedifferentiation and enhanced survival.
Indexed as
Identifiers
What OpenQuestion holds
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.