ArticleCell death and differentiation2019
Mutant p53-dependent mitochondrial metabolic alterations in a mesenchymal stem cell-based model of progressive malignancy.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Mutant p53 reactivation restricts the protumorigenic consequences of wild type p53 loss of heterozygosity in Li-Fraumeni syndrome patient-derived fibroblasts.Cell death and differentiation · 2024Article
- Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions.Biomolecules · 2024Review
- Phase separation of SHP2E76K promotes malignant transformation of mesenchymal stem cells by activating mitochondrial complexes.JCI insight · 2024Article
- Impact of glioma metabolism-related gene ALPK1 on tumor immune heterogeneity and the regulation of the TGF-β pathway.Frontiers in immunology · 2024Article
- Mesenchymal loss of p53 alters stem cell capacity and models human soft tissue sarcoma traits.Stem cell reports · 2023Article
- Current perspectives of mitochondria-targeted antioxidants in cancer prevention and treatment.Frontiers in cell and developmental biology · 2023Review
- Establishment and validation of a ferroptosis-related prognostic signature for hepatocellular carcinoma.Frontiers in oncology · 2023Article
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Review
- Modified Gold Nanoparticles to Overcome the Chemoresistance to Gemcitabine in Mutant p53 Cancer Cells.Pharmaceutics · 2021Article
- Global mapping of cancers: The Cancer Genome Atlas and beyond.Molecular oncology · 2021Review
- Serine and one-carbon metabolisms bring new therapeutic venues in prostate cancer.Discover oncology · 2021Review
- Guest edited collection: current friends and foes in gastrointestinal cancer.Discover oncology · 2021Article
- Recent advances in cancer immunotherapy.Discover oncology · 2021Review
- Understanding p53 tumour suppressor network.Biology direct · 2021Article
- NUAK2 and RCan2 participate in the p53 mutant pro-tumorigenic network.Biology direct · 2021Article
- Review
- Mutant p53 promotes RCP-dependent chemoresistance coinciding with increased delivery of P-glycoprotein to the plasma membrane.Cell death & disease · 2021Article
- A Novel Lactate Metabolism-Related Gene Signature for Predicting Clinical Outcome and Tumor Microenvironment in Hepatocellular Carcinoma.Frontiers in cell and developmental biology · 2021Article
- Clinical Value for Diagnosis and Prognosis of Signal Sequence Receptor 1 (SSR1) and Its Potential Mechanism in Hepatocellular Carcinoma: A Comprehensive Study Based on High-Throughput Data Analysis.International journal of general medicine · 2021Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well accepted that malignant transformation is associated with unique metabolism. Malignant transformation involves a variety of cellular pathways that are associated with initiation and progression of the malignant process that remain to be deciphered still. Here we used a mouse model of mutant p53 that presents a stepwise progressive transformation of adult Mesenchymal Stem Cells (MSCs). While the established parental p53Mut-MSCs induce tumors, the parental p53WT-MSCs that were established in parallel, did not. Furthermore, tumor lines derived from the parental p53Mut-MSCs (p53Mut-MSC-TLs), exhibited yet a more aggressive transformed phenotype, suggesting exacerbation in tumorigenesis. Metabolic tracing of these various cell types, indicated that while malignant transformation is echoed by a direct augmentation in glycolysis, the more aggressive p53Mut-MSC-TLs demonstrate increased mitochondrial oxidation that correlates with morphological changes in mitochondria mass and function. Finally, we show that these changes are p53Mut-dependent. Computational transcriptional analysis identified a mitochondrial gene signature specifically downregulated upon knock/out of p53Mut in MSC-TLs. Our results suggest that stem cells exhibiting different state of malignancy are also associated with a different quantitative and qualitative metabolic profile in a p53Mut-dependent manner. This may provide important insights for cancer prognosis and the use of specific metabolic inhibitors in a personalized designed cancer therapy.
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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.