ArticleOncogene2018
Gain-of-function mutant p53 promotes the oncogenic potential of head and neck squamous cell carcinoma cells by targeting the transcription factors FOXO3a and FOXM1.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 55 citations in OpenAlex.
- Context-DependentLaryngoscope investigative otolaryngology · 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
- Establishment and characterization of a new immortalized human oral keratinocyte (HOK) cell line harboring various TP53 mutations.Oral oncology · 2026Article
- The Multifaceted Role of p53 in Cancer Molecular Biology: Insights for Precision Diagnosis and Therapeutic Breakthroughs.Biomolecules · 2025Review
- The interplay between FOXO3 and FOXM1 influences sensitivity to AKT inhibition in PIK3CA and PIK3CA/PTEN altered estrogen receptor positive breast cancer.NPJ breast cancer · 2025Article
- Common Signaling Pathways in Cancer and Alzheimer's Disease May Point to New Treatments.Current topics in medicinal chemistry · 2025Review
- MiR-509-3p promotes gastric cancer development by activating FOXM1-mediated p38/MK2 pathway.Biomolecules & biomedicine · 2024Article
- From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.Biomarker research · 2024Review
- Mutant p53 gains oncogenic functions through a chromosomal instability-induced cytosolic DNA response.Nature communications · 2024Article
- Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review).Oncology reports · 2023Review
- Review
- Genomic landscape and gene expression profiles of feline oral squamous cell carcinoma.Frontiers in veterinary science · 2023Article
- Comprehensive analysis of lncRNA-mRNAs co-expression network identifies potential lncRNA biomarkers in cutaneous squamous cell carcinoma.BMC genomics · 2022Article
- Molecular Mechanisms of Cutaneous Squamous Cell Carcinoma.International journal of molecular sciences · 2022Review
- Pharmacologic inhibition of ataxia telangiectasia and Rad3-related (ATR) in the treatment of head and neck squamous cell carcinoma.Molecular carcinogenesis · 2022Review
- Article
- Construction of Bone Metastasis-Specific Regulation Network Based on Prognostic Stemness-Related Signatures in Prostate Cancer.Disease markers · 2022Article
- Genetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy.Frontiers in immunology · 2022Review
- New horizons in modulating the radio-sensitivity of head and neck cancer - 100 years after Warburg' effect discovery.Frontiers in oncology · 2022Review
- Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties that promote cancer cell invasive growth and metastasis, yet the mechanisms mediating these functions still largely remain elusive. We show here that overexpression of the GOF mutant p53 G245D and other GOF p53 mutants enhances the invasive cell growth of p53-deficient head and neck squamous cell carcinoma (HNSCC) UM-SCC-1 cells both in in vitro three-dimensional culture and in an in vivo orthotopic nude mouse model of HNSCC through a novel transcription-independent mechanism. We demonstrate that the expression of the oncogenic forkhead transcription factor FOXM1 is upregulated by GOF mutant p53s. Moreover, we show that overexpression of GOF mutant p53 G245D decreases the AMP-activated protein kinase (AMPK)-mediated phosphorylation of FOXO3a, a tumor suppressive forkhead transcription factor, leading to its cytoplasmic accumulation. This downregulation of FOXO3a's activity, in turn, leads to de-repression of FOXM1 expression. Importantly, we show that either overexpression of FOXO3a or downregulation of FOXM1 impairs both GOF mutant p53-mediated cell invasion in vitro and pulmonary metastases of UM-SCC-1 cells in vivo. Finally, not only do oral cancer patients with p53 mutations exhibit higher levels of FOXM1 expression than patients with wild-type p53, but also HNSCC patients with TP53 mutations and high levels of FOXM1 expression have the poorest survival outcomes. Given our prior demonstration that GOF mutant p53s inhibit AMPK, our current study, establishes and demonstrates a novel transcription-independent GOF mutant p53-AMPK-FOXO3a-FOXM1 signaling cascade that plays an important role in mediating mutant p53s' gain-of-function activities in HNSCCs.
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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.