ArticleCell death & disease2022
Inhibition of p21 activates Akt kinase to trigger ROS-induced autophagy and impacts on tumor growth rate.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 29 citations in OpenAlex.
- Fisetin Attenuates Amyloid-Beta-Induced Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells: Integrating In Silico Target Prediction and In Vitro Validation.Journal of biochemical and molecular toxicology · 2026Article
- DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation.EMBO reports · 2026Article
- Subcellular compartmentalization dependent dichotomy of p21 in cancer.Molecular biology reports · 2026Review
- 4-Hydroxychalcone Exert the Anti-cancer Potential in Colorectal Cancer Through Targeting CDK6.Biological procedures online · 2026Article
- The p21 resilience network: a conceptual framework linking senescence to ferroptosis and cuproptosis resistance.NPJ systems biology and applications · 2026Review
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- CDKN1A/p21 Influences the Survival and Expansion of Breast Cancer Stem Cells after Oxidative Damage.Oncology research · 2026Article
- p53 Orchestrates the Immunogenic-Tolerogenic Pyroptosis Switch in Non-Small Cell Lung Cancer: A Systems Biology Approach.Computational and structural biotechnology journal · 2026Article
- LINC02081 as an oncogene promotes cell proliferation and G2/M cycle through p53 signaling pathway in lung adenocarcinoma.Translational cancer research · 2025Article
- BRSK2 plays a role in autophagy and cancer cell growth and survival under nutrient deprivation stress via the PIK3C3 pathway.Scientific reports · 2025Article
- Review
- Vismodegib Potentiates Marine Antimicrobial Peptide Tilapia Piscidin 4-Induced Cytotoxicity in Human Non-Small Cell Lung Cancer Cells.Probiotics and antimicrobial proteins · 2025Article
- Regulation of Autophagy by the Cdk1/p53/p21 Feedback Loop in an Interstitial Cystitis/Bladder Pain Syndrome Cell Model: Implications for Inflammatory Response.International urogynecology journal · 2025Article
- Regulation of PD-L1 Expression by SAHA-Mediated Histone Deacetylase Inhibition in Lung Cancer Cells.Cancers · 2025Article
- LncRNA TMEM99 Complexes with IGF2BP2 to Inhibit Autophagy in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Reply to "Letter to the Editor: Targeted Inhibition of p21 Promotes the Growth of Breast Cancer Cells and Impairs the Tumor-Killing Effect of the Vaccinia Virus".Journal of breast cancer · 2025Article
- Bisphenol A suppresses colon epithelial cell responses via GScientific reports · 2025Article
- hERG activators exhibit antitumor effects in breast cancer through calcineurin and β-catenin-mediated signaling pathways.Frontiers in pharmacology · 2025Article
- The Emerging Role of p21 in Diabetes and Related Metabolic Disorders.International journal of molecular sciences · 2024Review
- Targeted Inhibition of p21 Promotes the Growth of Breast Cancer Cells and Impairs the Tumor-Killing Effect of the Vaccinia Virus.Journal of breast cancer · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Owing to its ability to induce cellular senescence, inhibit PCNA, and arrest cell division cycle by negatively regulating CDKs as well as being a primary target of p53, p21 is traditionally considered a tumor suppressor. Nonetheless, several reports in recent years demonstrated its pro-oncogenic activities such as apoptosis inhibition by cytosolic p21, stimulation of cell motility, and promoting assembly of cyclin D-CDK4/6 complex. These opposing effects of p21 on cell proliferation, supported by the observations of its inconsistent expression in human cancers, led to the emergence of the concept of "antagonistic duality" of p21 in cancer progression. Here we demonstrate that p21 negatively regulates basal autophagy at physiological concentration. Akt activation, upon p21 attenuation, driven ROS accumulation appears to be the major underlying mechanism in p21-mediated modulation of autophagy. We also find p21, as a physiological inhibitor of autophagy, to have oncogenic activity during early events of tumor development while its inhibition favors survival and growth of cancer cells in the established tumor. Our data, thereby, reveal the potential role of autophagy in antagonistic functional duality of p21 in cancer.
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.