ArticleCancer discovery2024
Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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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
63 citing papers in PubMed, 82 citations in OpenAlex.
- Article
- Mutant p53 gains RNA-binding activity to reprogram translation and mitochondrial function.Cell reports · 2026Article
- Oncogenic p53 induces mitotic errors in lung cancer cells by recopying DNA replication forks conferring targetable proliferation advantage.Cell death and differentiation · 2026Article
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- p53 mutation-associated prognosis across cancer types underlines hematological malignancy as an applicable cancer type to p53-rescue therapy.Fundamental research · 2026Article
- TP53 mutation at codon 179 metabolically reprograms cancer cells to promote invasion.Cancer gene therapy · 2026Article
- Integrating DNA Mutations and RNA Expression of Cancer Driver Genes in Asian Rare Cancers: A Pan-Cancer Analysis.JCO precision oncology · 2026Article
- Metabolic adaptation to IMMT deficiency through the ATF6-PPARγ axis is contingent on TP53 mutation status in breast cancer.Cell death & disease · 2026Article
- Low-penetrance TP53 variants are mainly hypomorphic: an underestimated issue with high clinical significance.NPJ genomic medicine · 2026Article
- Multiple ETS family transcription factors bind mutant p53 via distinct interaction regions.FEBS letters · 2026Article
- Tumor exosomes impact functional hallmarks of cancer.Cancer metastasis reviews · 2026Review
- Evaluation of non-canonical p53 functions in DNA replication and recombination for variant classification.Cell death & disease · 2026Article
- Review
- Tumor suppressor genes and KRAS G12C inhibitor resistance in non-small cell lung cancer.iScience · 2026Review
- Ribosome biogenesis programs define a three-gene RBscore with prognostic relevance in bladder cancer.Frontiers in immunology · 2026Article
- EGFR-targeted affibody-polyIC polyplex kills EGFR-overexpressing cancer cells without activating the EGFR.PloS one · 2026Article
- GSG2 promotes aerobic glycolysis and colorectal cancer progression via the MDM2-p53 axis.American journal of cancer research · 2026Article
- p53 inactivation drives breast cancer metastasis to the brain through SCD1 upregulation and increased fatty acid metabolism.Nature genetics · 2026Article
- Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.Theranostics · 2026Review
- The guardian of the genome meets immunotherapy: p53-based strategies.Frontiers in immunology · 2026Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutations in the tumor suppressor TP53 cause cancer and impart poor chemotherapeutic responses, reportedly through loss-of-function, dominant-negative effects and gain-of-function (GOF) activities. The relative contributions of these attributes is unknown. We found that removal of 12 different TP53 mutants with reported GOFs by CRISPR/Cas9 did not impact proliferation and response to chemotherapeutics of 15 human cancer cell lines and colon cancer-derived organoids in culture. Moreover, removal of mutant TP53/TRP53 did not impair growth or metastasis of human cancers in immune-deficient mice or growth of murine cancers in immune-competent mice. DepMap mining revealed that removal of 158 different TP53 mutants had no impact on the growth of 391 human cancer cell lines. In contrast, CRISPR-mediated restoration of wild-type TP53 extinguished the growth of human cancer cells in vitro. These findings demonstrate that LOF but not GOF effects of mutant TP53/TRP53 are critical to sustain expansion of many tumor types. SIGNIFICANCE: This study provides evidence that removal of mutant TP53, thereby deleting its reported GOF activities, does not impact the survival, proliferation, metastasis, or chemotherapy responses of cancer cells. Thus, approaches that abrogate expression of mutant TP53 or target its reported GOF activities are unlikely to exert therapeutic impact in cancer. See related commentary by Lane, p. 211 . This article is featured in Selected Articles from This Issue, p. 201.
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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.