ArticlePLoS pathogens2019
Autocrine STAT3 activation in HPV positive cervical cancer through a virus-driven Rac1-NFκB-IL-6 signalling axis.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 136 citations in OpenAlex.
- Review
- The Dual Role of Interleukin-6 in the Pathophysiology of Skeletal Muscle: Mechanisms, Challenges, and Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2026Review
- b-AP15 enhances TRAIL-induced cell death in HNSCC via the induction of ROS/JNK/DR5 signalling.Cancer gene therapy · 2026Article
- Targeting STAT3 Promotes Tumor Cell Death and Enhances T-Cell Activity in HPV16-Positive Cancer.Cancers · 2026Article
- Transcriptional modulation of the PI3K/AKT/mTOR signaling pathway mediated by HPV16Exploration of targeted anti-tumor therapy · 2026Article
- Circular RNAs in cervical cancer: from ceRNA networks to epitranscriptomic regulation, immune modulation, and metastatic reprogramming.Frontiers in immunology · 2026Review
- A mitochondrial regulatory network of ferroptosis defense in HPV-positive cervical cancer: therapeutic implications of the mitoSTAT3-DHODH axis.Frontiers in pharmacology · 2026Review
- The microbiota-host metabolic axis in cervical cancer: from homeostatic disruption to mechanisms of therapy resistance.Frontiers in cellular and infection microbiology · 2026Review
- Topoisomerase IIα orchestrates secretion of IL-6 and IL-8 with human papillomavirus replication.Virologica Sinica · 2025Article
- Hypoxia drives cervical cancer progression via OCT4/ORAI3-dependent glycolysis and CaCellular and molecular life sciences : CMLS · 2025Article
- 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
- WNK1 promotes head and neck squamous cell carcinoma progression through activation of NF-κB signaling pathway.Discover oncology · 2025Article
- HPV as a Molecular Hacker: Computational Exploration of HPV-Driven Changes in Host Regulatory Networks.Viruses · 2025Article
- HPV16 E6 and E7 expressing cancer cells suppress the antitumor immune response by upregulating KLF2-mediated IL-23 expression in macrophages.Journal for immunotherapy of cancer · 2025Article
- Research on the regulatory effects and mechanisms of YES1 on apoptosis and autophagy in cervical cancer cells.Discover oncology · 2025Article
- Predictive and prognostic value of inflammatory factors (IL-6, IL-8, and TNF-α) in saliva for radiotherapy response in patients with HPV-associated oropharyngeal squamous cell carcinoma.Discover oncology · 2025Article
- Advances in understanding the mechanisms of the human papillomavirus oncoproteins.Biochemical Society transactions · 2025Review
- The Differential Expression of the JAK/STAT Pathway in Breast Cancer Cells Transfected with Human Papillomavirus Oncogenes.Viruses · 2025Article
- YAP controls cell migration and invasion through a Rho GTPase switch.Science signaling · 2025Article
- Review
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Persistent human papillomavirus (HPV) infection is the leading cause of cervical cancer. Although the fundamental link between HPV infection and oncogenesis is established, the specific mechanisms of virus-mediated transformation are not fully understood. We previously demonstrated that the HPV encoded E6 protein increases the activity of the proto-oncogenic transcription factor STAT3 in primary human keratinocytes; however, the molecular basis for STAT3 activation in cervical cancer remains unclear. Here, we show that STAT3 phosphorylation in HPV positive cervical cancer cells is mediated primarily via autocrine activation by the pro-inflammatory cytokine Interleukin 6 (IL-6). Antibody-mediated blockade of IL-6 signalling in HPV positive cells inhibits STAT3 phosphorylation, whereas both recombinant IL-6 and conditioned media from HPV positive cells leads to increased STAT3 phosphorylation within HPV negative cervical cancer cells. Interestingly, we demonstrate that activation of the transcription factor NFκB, involving the small GTPase Rac1, is required for IL-6 production and subsequent STAT3 activation. Our data provides new insights into the molecular re-wiring of cancer cells by HPV E6. We reveal that activation of an IL-6 signalling axis drives the autocrine and paracrine phosphorylation of STAT3 within HPV positive cervical cancers cells and that activation of this pathway is essential for cervical cancer cell proliferation and survival. Greater understanding of this pathway provides a potential opportunity for the use of existing clinically approved drugs for the treatment of HPV-mediated cervical cancer.
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