ArticlePLoS pathogens2018
STAT3 activation by E6 is essential for the differentiation-dependent HPV18 life cycle.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 92 citations in OpenAlex.
- Plant Bioactive Constituents and Their Potential Benefits in HPV-Positive Oropharyngeal Squamous Cell Carcinoma-A Narrative Review.Current issues in molecular biology · 2026Review
- A mitochondrial regulatory network of ferroptosis defense in HPV-positive cervical cancer: therapeutic implications of the mitoSTAT3-DHODH axis.Frontiers in pharmacology · 2026Review
- Attributes of HPV associated cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Insights into expression and localization of HPV16 LCR-associated transcription factors and association with LCR activity in HNSCC.Molecular therapy. Oncology · 2025Article
- Article
- HPV-driven transcriptome and splicing rewiring under SRPK1 inhibition in cervical cancer.Frontiers in oncology · 2025Article
- The roles of DNA damage repair and innate immune surveillance pathways in HPV pathogenesis.Virology · 2024Review
- E7-mediated repression of miR-203 promotes LASP1-dependent proliferation in HPV-positive cervical cancer.Oncogene · 2024Article
- The Immune Response of Cancer Cells in Breast and Gynecologic Neoplasms.International journal of molecular sciences · 2024Review
- Review
- Talin-1 inhibits Smurf1-mediated Stat3 degradation to modulate β-cell proliferation and mass in mice.Cell death & disease · 2023Article
- Nuclear proinflammatory cytokine S100A9 enhances expression of human papillomavirus oncogenes via transcription factor TEAD1.Journal of virology · 2023Article
- Exploitation of ATP-sensitive potassium ion (KOncogene · 2023Article
- CREB1 activation promotes human papillomavirus oncogene expression and cervical cancer cell transformation.Journal of medical virology · 2023Article
- Herpes Simplex Virus, Human Papillomavirus, and Cervical Cancer: Overview, Relationship, and Treatment Implications.Cancers · 2023Review
- Review
- Exploring the Bioactive Mycocompounds (Fungal Compounds) of Selected Medicinal Mushrooms and Their Potentials against HPV Infection and Associated Cancer in Humans.Life (Basel, Switzerland) · 2023Review
- Article
- Investigation of molecular mechanisms underlying JAK/STAT signaling pathway in HPV-induced cervical carcinogenesis using 'omics' approach.Medical oncology (Northwood, London, England) · 2022Article
- The First Human Vulvar Intraepithelial Neoplasia Cell Line with Naturally Infected Episomal HPV18 Genome.Viruses · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Human papillomaviruses (HPV) activate a number of host factors to control their differentiation-dependent life cycles. The transcription factor signal transducer and activator of transcription (STAT)-3 is important for cell cycle progression and cell survival in response to cytokines and growth factors. STAT3 requires phosphorylation on Ser727, in addition to phosphorylation on Tyr705 to be transcriptionally active. In this study, we show that STAT3 is essential for the HPV life cycle in undifferentiated and differentiated keratinocytes. Primary human keratinocytes containing high-risk HPV18 genomes display enhanced STAT3 phosphorylation compared to normal keratinocytes. Expression of the E6 oncoprotein is sufficient to induce the dual phosphorylation of STAT3 at Ser727 and Tyr705 by a mechanism requiring Janus kinases and members of the MAPK family. E6-mediated activation of STAT3 induces the transcription of STAT3 responsive genes including cyclin D1 and Bcl-xL. Silencing of STAT3 protein expression by siRNA or inhibition of STAT3 activation by small molecule inhibitors, or by expression of dominant negative STAT3 phosphorylation site mutants, results in blockade of cell cycle progression. Loss of active STAT3 impairs HPV gene expression and prevents episome maintenance in undifferentiated keratinocytes and upon differentiation, lack of active STAT3 abolishes virus genome amplification and late gene expression. Organotypic raft cultures of HPV18 containing keratinocytes expressing a phosphorylation site STAT3 mutant display a profound reduction in suprabasal hyperplasia, which correlates with a loss of cyclin B1 expression and increased differentiation. Finally, increased STAT3 expression and phosphorylation is observed in HPV positive cervical disease biopsies compared to control samples, highlighting a role for STAT3 activation in cervical carcinogenesis. In summary, our data provides evidence of a critical role for STAT3 in the HPV18 life cycle.
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Registered trials
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