ArticleMolecular oncology2017
Gain-of-function p53 activates multiple signaling pathways to induce oncogenicity in lung cancer cells.
Article in Molecular oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Oncogenic p53 induces mitotic errors in lung cancer cells by recopying DNA replication forks conferring targetable proliferation advantage.Cell death and differentiation · 2026Article
- Molecular Characteristics and Treatment Implications of TP53 Gain-of-Function Mutations in Non-Small Cell Lung Cancer.Cancer medicine · 2025Article
- Mutant p53 Gain of Function: Why Many See It, Why Some Do Not.Cancer discovery · 2025Article
- Rewired mNature communications · 2023Article
- Article
- The oncogenicity of tumor-derived mutant p53 is enhanced by the recruitment of PLK3.Nature communications · 2021Article
- Prediction of Overall Survival Among Female Patients With Breast Cancer Using a Prognostic Signature Based on 8 DNA Repair-Related Genes.JAMA network open · 2020Article
- Gain-of-Function Mutations: An Emerging Advantage for Cancer Biology.Trends in biochemical sciences · 2019Review
- Smyd2 conformational changes in response to p53 binding: role of the C-terminal domain.Molecular oncology · 2019Article
- p63 at the Crossroads between Stemness and Metastasis in Breast Cancer.International journal of molecular sciences · 2019Review
- ΔNp63 in squamous cell carcinoma: defining the oncogenic routes affecting epigenetic landscape and tumour microenvironment.Molecular oncology · 2019Review
- Diverse and cancer type‑specific roles of the p53 R248Q gain‑of‑function mutation in cancer migration and invasiveness.International journal of oncology · 2019Article
- Aberrant expression of ETS1 and ETS2 proteins in cancer.Cancer reports and reviews · 2018Article
- 3D culture technologies of cancer stem cells: promising ex vivo tumor models.Journal of tissue engineeringReview
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Gain-of-function (GOF) mutants of p53 upregulate genes implicated in cell proliferation and oncogenesis. Here, we report that GOF p53 induces tumorigenicity through simultaneous activation of key oncogenic pathways including those controlling putative tumor-initiating cell functions. We determined that in cells expressing p53-R273H, GOF p53 simultaneously upregulates genes from multiple signaling pathways by recognizing promoters containing distinct transcription factor (TF) binding sites. Our analytical data support a model in which GOF p53 complexes with two TFs on the promoter-a mediator protein, Med17, and a histone acetyl transferase, activating histone acetylation-and enhances gene expression to signal cell proliferation and oncogenesis. Thus, therapeutic inhibition of one GOF p53-induced pathway would be insufficient to prevent tumor growth as the oncoprotein activates a multitude of parallel pathways. This discovery suggests enormous selection advantage for cancer cells with GOF p53 to induce oncogenic growth, highlighting the problems of cancer therapy.
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