ArticleCell death & disease2014
Unequal prognostic potentials of p53 gain-of-function mutations in human cancers associate with drug-metabolizing activity.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 95 citations in OpenAlex.
- Clonal Evolutionary Analysis during HER2 Blockade in HER2-Positive Inflammatory Breast Cancer: A Phase II Open-Label Clinical Trial of Afatinib +/- Vinorelbine.PLoS medicine · 2016Trial
- Elf3 drives β-catenin transactivation and associates with poor prognosis in colorectal cancer.Cell death & disease · 2014Trial
- TP53 mutation at codon 179 metabolically reprograms cancer cells to promote invasion.Cancer gene therapy · 2026Article
- Covalent drug rescue of multiple p53 mutants by stabilizing vinyl sulfone fragments hints to a specific refolding mechanism for R282W.Protein science : a publication of the Protein Society · 2026Article
- Genomic Enrichment and Functional Impact of TP53 and CYLD Alterations in Recurrent and Metastatic HPV-Associated Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Development and validation of manganese metabolism-related genes prognostic model in colorectal cancer and its immunological characteristics.Journal of gastrointestinal oncology · 2026Article
- Targeting the JAK2-STAT3-UCHL3-ENO1 axis suppresses glycolysis and enhances the sensitivity to 5-FU chemotherapy inActa pharmaceutica Sinica. B · 2025Article
- [Next generation sequencing (NGS)-based molecular panel analysis for metastatic prostate cancer: how often can we detect druggable mutations? : NGS for metastatic adenocarcinoma of the prostate].Urologie (Heidelberg, Germany) · 2025Article
- The Role of p53 Mutations in Early and Late Response to Mitotic Aberrations.Biomolecules · 2025Review
- Efficacy of Wee1 G2 Checkpoint Kinase and Mouse Double Minute 2 Homolog Inhibitors in Gastrointestinal Stromal Tumors Determined by p53 Status.Oncology research · 2025Article
- Predictive value ofThe veterinary quarterly · 2024Article
- Effect of PAWI-2 on pancreatic cancer stem cell tumors.Investigational new drugs · 2024Article
- TP53 gain-of-function mutations promote osimertinib resistance via TNF-α-NF-κB signaling in EGFR-mutated lung cancer.NPJ precision oncology · 2024Article
- Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.Cancer communications (London, England) · 2024Review
- Multidimensional quantitative phenotypic and molecular analysis reveals neomorphic behaviors of p53 missense mutants.NPJ breast cancer · 2023Article
- In-silico analysis of TCGA data showing multiple POLE-like favourable subgroups overlapping with TP53 mutated endometrial cancer: Implications for clinical practice in low and middle-income countries.Gynecologic oncology reports · 2023Article
- Progressive metastatic infantile fibrosarcoma with multiple acquired mutations.Cold Spring Harbor molecular case studies · 2023Article
- Racial and ethnic differences in type II endometrial cancer mortality outcomes: The contribution of sociodemographic, clinicopathologic, and treatment factors.Gynecologic oncology · 2023Article
- GOF Mutant p53 in Cancers: A Therapeutic Challenge.Cancers · 2022Review
- Anticancer Therapeutic Strategies Targeting p53 Aggregation.International journal of molecular sciences · 2022Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutation of p53 is the most common genetic change in human cancer, causing complex effects including not only loss of wild-type function but also gain of novel oncogenic functions (GOF). It is increasingly likely that p53-hotspot mutations may confer different types and magnitudes of GOF, but the evidences are mainly supported by cellular and transgenic animal models. Here we combine large-scale cancer genomic data to characterize the prognostic significance of different p53 mutations in human cancers. Unexpectedly, only mutations on the Arg248 and Arg282 positions displayed significant association with shorter patient survival, but such association was not evident for other hotspot GOF mutations. Gene set enrichment analysis on these mutations revealed higher activity of drug-metabolizing enzymes, including the CYP3A4 cytochrome P450. Ectopic expression of p53 mutant R282W in H1299 and SaOS2 cells significantly upregulated CYP3A4 mRNA and protein levels, and cancer cell lines bearing mortality-associated p53 mutations display higher CYP3A4 expression and resistance to several CYP3A4-metabolized chemotherapeutic drugs. Our results suggest that p53 mutations have unequal GOF activities in human cancers, and future evaluation of p53 as a cancer biomarker should consider which mutation is present in the tumor, rather than having comparison between wild-type and mutant genotypes.
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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.