ArticleMolecular oncology2016
Mutant p53 proteins counteract autophagic mechanism sensitizing cancer cells to mTOR inhibition.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 97 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Pathogenesis of Penile Squamous Cell Carcinoma: Molecular Update and Systematic Review.International journal of molecular sciences · 2021Pooled it
- A Randomized Multi-institutional Phase II Trial of Everolimus as Adjuvant Therapy in Patients with Locally Advanced Squamous Cell Cancer of the Head and Neck.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- mTOR inhibition augments antitumor immune effector response by reprogramming thebioRxiv : the preprint server for biology · 2026Article
- Regulation of autophagy by the p53 family and the implications for cancer therapies.Discover oncology · 2026Review
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- TP53 Loss Fuels mTORC1 Activation and Autophagy Suppression to Drive Immune-Cold Colorectal Cancer.World journal of oncology · 2026Article
- Multiple roles of p53 in cancer development: Regulation of tumor microenvironment, mJournal of advanced research · 2025Review
- Decoding the dual role of autophagy in cancer through transcriptional and epigenetic regulation.FEBS letters · 2025Review
- Review
- Mechanistic insights and therapeutic strategies for targeting autophagy in pancreatic ductal adenocarcinoma.Discover oncology · 2025Review
- Review
- Antitumor effects and mechanisms of traditional Chinese medicine gamboge: A review.Frontiers in pharmacology · 2025Review
- Polo-like kinase 2 targeting as novel strategy to sensitize mutant p53-expressing tumor cells to anticancer treatments.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Kinase activities in pancreatic ductal adenocarcinoma with prognostic and therapeutic avenues.Molecular oncology · 2024Article
- ATF6 supports lysosomal function in tumor cells to enable ER stress-activated macroautophagy and CMA: impact on mutant TP53 expression.Autophagy · 2024Article
- Post-Translational Modifications (PTMs) of mutp53 and Epigenetic Changes Induced by mutp53.Biology · 2024Review
- Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions.Biomolecules · 2024Review
- p53 modulates kinase inhibitor resistance and lineage plasticity in NF1-related MPNSTs.Oncogene · 2024Article
- Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.Cancer communications (London, England) · 2024Review
- The Roles of Autophagy-related miRNAs in Gynecologic Tumors: A Review of Current Knowledge for Possible Targeted Therapy.Current molecular medicine · 2024Review
37 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in TP53 gene play a pivotal role in tumorigenesis and cancer development. Here, we report that gain-of-function mutant p53 proteins inhibit the autophagic pathway favoring antiapoptotic effects as well as proliferation of pancreas and breast cancer cells. We found that mutant p53 significantly counteracts the formation of autophagic vesicles and their fusion with lysosomes throughout the repression of some key autophagy-related proteins and enzymes as BECN1 (and P-BECN1), DRAM1, ATG12, SESN1/2 and P-AMPK with the concomitant stimulation of mTOR signaling. As a paradigm of this mechanism, we show that atg12 gene repression was mediated by the recruitment of the p50 NF-κB/mutant p53 protein complex onto the atg12 promoter. Either mutant p53 or p50 NF-κB depletion downregulates atg12 gene expression. We further correlated the low expression levels of autophagic genes (atg12, becn1, sesn1, and dram1) with a reduced relapse free survival (RFS) and distant metastasis free survival (DMFS) of breast cancer patients carrying TP53 gene mutations conferring a prognostic value to this mutant p53-and autophagy-related signature. Interestingly, the mutant p53-driven mTOR stimulation sensitized cancer cells to the treatment with the mTOR inhibitor everolimus. All these results reveal a novel mechanism through which mutant p53 proteins promote cancer cell proliferation with the concomitant inhibition of autophagy.
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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.