ArticleOncotarget2016
Human papillomavirus oncogenic E6 protein regulates human β-defensin 3 (hBD3) expression via the tumor suppressor protein p53.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Molecular Behavior of Human β Defensin Type 3 Embedded in Different Model Lipid Membranes.Journal of chemical information and modeling · 2026Article
- Advances in the Role of Antimicrobial Peptides in the Management of Sexually Transmitted Infections.Journal of clinical laboratory analysis · 2025Review
- HPV16 E7 inhibits HBD2 expression by down-regulation of ASK1-p38 MAPK pathway in cervical cancer.Virology journal · 2025Article
- Pioneering Clinical Investigation: Beta Defensin Expression in Patients of Squamous Cell Carcinoma of Oral Cavity as a Forward-Looking Validation for Molecular Treatment.Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India · 2025Article
- Understanding the Dynamics of Human Defensin Antimicrobial Peptides: Pathogen Resistance and Commensal Induction.Applied biochemistry and biotechnology · 2024Review
- Review
- Beta-defensin index: A functional biomarker for oral cancer detection.Cell reports. Medicine · 2024Article
- Role of Defensins in Tumor Biology.International journal of molecular sciences · 2023Review
- Defensins: defenders of human reproductive health.Human reproduction update · 2023Review
- HPV infection alters vaginal microbiome through down-regulating host mucosal innate peptides used by Lactobacilli as amino acid sources.Nature communications · 2022Article
- The Interplay Between Cervicovaginal Microbial Dysbiosis and Cervicovaginal Immunity.Frontiers in immunology · 2022Review
- Deoxyshikonin-Induced Gene Expression Profile in Porcine Epithelial Cells.Frontiers in veterinary science · 2021Article
- Elevated serum levels of cathelicidin and β-defensin 2 are associated with basal cell carcinoma.Central-European journal of immunology · 2021Article
- Defensins: A Double-Edged Sword in Host Immunity.Frontiers in immunology · 2020Review
- HBD3 Induces PD-L1 Expression on Head and Neck Squamous Cell Carcinoma Cell Lines.Antibiotics (Basel, Switzerland) · 2019Article
- Human Beta Defensins and Cancer: Contradictions and Common Ground.Frontiers in oncology · 2019Review
- Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA.Nature communications · 2018Article
- Epidermal Growth Factor (EGF) Autocrine Activation of Human Platelets Promotes EGF Receptor-Dependent Oral Squamous Cell Carcinoma Invasion, Migration, and Epithelial Mesenchymal Transition.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Low risk HPV-6E6 induces apoptosis in bone marrow-derived dendritic cells.Oncology letters · 2018Article
- Alarmins and immunity.Immunological reviews · 2017Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Human β-defensin-3 (hBD3) is an epithelial cell-derived innate immune regulatory molecule overexpressed in oral dysplastic lesions and fosters a tumor-promoting microenvironment. Expression of hBD3 is induced by the epidermal growth factor receptor signaling pathway. Here we describe a novel pathway through which the high-risk human papillomavirus type-16 (HPV-16) oncoprotein E6 induces hBD3 expression in mucosal keratinocytes. Ablation of E6 by siRNA induces the tumor suppressor p53 and diminishes hBD3 in HPV-16 positive CaSki cervical cancer cells and UM-SCC-104 head and neck cancer cells. Malignant cells in HPV-16-associated oropharyngeal cancer overexpress hBD3. HPV-16 E6 induces hBD3 mRNA expression, peptide production and gene promoter activity in mucosal keratinocytes. Reduction of cellular levels of p53 stimulates hBD3 expression, while activation of p53 by doxorubicin inhibits its expression in primary oral keratinocytes and CaSki cells, suggesting that p53 represses hBD3 expression. A p53 binding site in the hBD3 gene promoter has been identified by using electrophoretic mobility shift assays and chromatin immunoprecipitation (ChIP). In addition, the p63 protein isoform ΔNp63α, but not TAp63, stimulated transactivation of the hBD3 gene and was co-expressed with hBD3 in head and neck cancer specimens. Therefore, high-risk HPV E6 oncoproteins may stimulate hBD3 expression in tumor cells to facilitate tumorigenesis of HPV-associated head and neck cancer.
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