ArticleProceedings of the National Academy of Sciences of the United States of America2017
ΔNp63-mediated regulation of hyaluronic acid metabolism and signaling supports HNSCC tumorigenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
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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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- The Stem Cell Expression Profile of Odontogenic Tumors and Cysts: A Systematic Review and Meta-Analysis.Genes · 2023Pooled it
- Article
- ATF6α inhibits ΔNp63α expression to promote breast cancer metastasis by the GRP78-AKT1-FOXO3a signaling.Cell death & disease · 2025Article
- Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential.Molecular oncology · 2024Review
- ABCC1 Is a ΔNp63 Target Gene Overexpressed in Squamous Cell Carcinoma.International journal of molecular sciences · 2024Article
- Role of Stem Cells in the Pathogenesis and Malignant Transformation of Oral Submucous Fibrosis.Stem cell reviews and reports · 2024Review
- Deciphering Drug Resistance: Investigating the Emerging Role of Hyaluronan Metabolism and Signaling and Tumor Extracellular Matrix in Cancer Chemotherapy.International journal of molecular sciences · 2024Review
- Gene-Expression Patterns of Tumor and Peritumor Tissues of Smoking and Non-Smoking HPV-Negative Patients with Head and Neck Squamous Cell Carcinoma.Biomedicines · 2024Article
- p63 orchestrates serine and one carbon metabolism enzymes expression in head and neck cancer.Biology direct · 2023Article
- Mesenchymal stromal cells confer breast cancer doxorubicin resistance by producing hyaluronan.Oncogene · 2023Article
- Article
- The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation.Nature communications · 2023Article
- Development of a Novel Anti-CD44 Variant 5 Monoclonal Antibody CAntibodies (Basel, Switzerland) · 2023Article
- Development of a Novel Anti-CD44 Variant 7/8 Monoclonal Antibody, CBiomedicines · 2023Article
- Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments.Molecular cancer · 2023Review
- Targeted therapy for head and neck cancer: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Distinct interactors define the p63 transcriptional signature in epithelial development or cancer.The Biochemical journal · 2022Article
- ΔNp63-Senataxin circuit controls keratinocyte differentiation by promoting the transcriptional termination of epidermal genes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Gain-of-function hot spot mutant p53Translational oncology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and several molecular pathways that underlie the molecular tumorigenesis of HNSCC have been identified. Among them, amplification or overexpression of ΔNp63 isoforms is observed in the majority of HNSCCs. Here, we unveiled a ΔNp63-dependent transcriptional program able to regulate the metabolism and the signaling of hyaluronic acid (HA), the major component of the extracellular matrix (ECM). We found that ∆Np63 is capable of sustaining the production of HA levels in cell culture and in vivo by regulating the expression of the HA synthase HAS3 and two hyaluronidase genes, HYAL-1 and HYAL-3. In addition, ∆Np63 directly regulates the expression of CD44, the major HA cell membrane receptor. By controlling this transcriptional program, ∆Np63 sustains the epithelial growth factor receptor (EGF-R) activation and the expression of ABCC1 multidrug transporter gene, thus contributing to tumor cell proliferation and chemoresistance. Importantly, p63 expression is positively correlated with CD44, HAS3, and ABCC1 expression in squamous cell carcinoma datasets and p63-HA pathway is a negative prognostic factor of HNSCC patient survival. Altogether, our data shed light on a ∆Np63-dependent pathway functionally important to the regulation of HNSCC progression.
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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.