ArticleProceedings of the National Academy of Sciences of the United States of America2015
Molecular transitions from papillomavirus infection to cervical precancer and cancer: Role of stromal estrogen receptor signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
184 citing papers in PubMed, 3 syntheses or guidelines pooled it, 307 citations in OpenAlex.
- Meta-Analysis of Polymorphic Variants Conferring Genetic Risk to Cervical Cancer in Indian Women Supports CYP1A1 as an Important Associated LocusAsian Pacific journal of cancer prevention : APJCP · 2018Pooled it
- Integrated analysis reveals down-regulation of SPARCL1 is correlated with cervical cancer development and progression.Cancer biomarkers : section A of Disease markers · 2018Pooled it
- Pooled it
- The ESR1-MYH14 axis functions as a critical driver of cervical cancer progression and metastasis.Translational oncology · 2026Article
- The Role of Sex Hormone Receptors in the Squamous Cell Carcinoma of the Uterine Ectocervix: A Review and Future Directions.Diagnostics (Basel, Switzerland) · 2026Review
- Lactylation-based machine algorithm combined with multi-omics analysis to predict prognosis in cervical cancer.Oncology letters · 2026Article
- When Estrogen Signaling Refuses to Die: Receptor Rewiring, Compartmentalization, and Endocrine Plasticity in Gynecological Cancers.International journal of molecular sciences · 2026Review
- Identification and mechanistic exploration of VEGFA and CALML3 as calcium channel-related prognostic genes in cervical cancer.Discover oncology · 2026Article
- Precision Biomarker Identification in Gynecological Cancers Using Coexpression Networks and Attention-Based LSTM in Healthcare 4.0.Diagnostics (Basel, Switzerland) · 2026Article
- MCell death & disease · 2026Article
- Estrogen receptor α expression in tumor-infiltrating lymphocytes from patients with endometrial cancer.Oncology letters · 2026Article
- Single-Cell Transcriptomic Landscape of Cervical Cancer Cell Lines Before and After Chemoradiotherapy.Cells · 2026Article
- Signaling pathways and targeted interventions for precancers.Signal transduction and targeted therapy · 2026Review
- Exploring the molecular basis ofBioinformatics advances · 2026Article
- Role of mucosal chemokines in the development of tissue-resident CD4Frontiers in immunology · 2026Review
- The Role of HPV and Hormone in Cervical Precancer and Cancer: Molecular Pathophysiology and Cell Biology of Disease and Treatment.Oncology research · 2026Review
- A nomogram model integrating transcriptomics and clinical features for predicting the risk of cervical intraepithelial lesion progression.Frontiers in oncology · 2026Article
- Systems Vaccinology-Integrated Proteomics to Develop a Novel Prophylactic and Therapeutic Vaccine Against Human Papillomavirus 16.Bioinformatics and biology insights · 2026Article
- Let-7c/RUNX1 Axis Promotes Cervical Cancer: A Bioinformatic Analysis.Current issues in molecular biology · 2025Article
- Predictive value of MHC-related genes in cervical cancer: implications for immunotherapy and prognostic nomogram development.Discover oncology · 2025Article
124 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 1 country.
Funding
Abstract
To study the multistep process of cervical cancer development, we analyzed 128 frozen cervical samples spanning normalcy, increasingly severe cervical intraepithelial neoplasia (CIN1- CIN3), and cervical cancer (CxCa) from multiple perspectives, revealing a cascade of progressive changes. Compared with normal tissue, expression of many DNA replication/repair and cell proliferation genes was increased in CIN1/CIN2 lesions and further sustained in CIN3, consistent with high-risk human papillomavirus (HPV)-induced tumor suppressor inactivation. The CIN3-to-CxCa transition showed metabolic shifts, including decreased expression of mitochondrial electron transport complex components and ribosomal protein genes. Significantly, despite clinical, epidemiological, and animal model results linking estrogen and estrogen receptor alpha (ERα) to CxCa, ERα expression declined >15-fold from normalcy to cancer, showing the strongest inverse correlation of any gene with the increasing expression of p16, a marker for HPV-linked cancers. This drop in ERα in CIN and tumor cells was confirmed at the protein level. However, ERα expression in stromal cells continued throughout CxCa development. Our further studies localized stromal ERα to FSP1+, CD34+, SMA- precursor fibrocytes adjacent to normal and precancerous CIN epithelium, and FSP1-, CD34-, SMA+ activated fibroblasts in CxCas. Moreover, rank correlations with ERα mRNA identified IL-8, CXCL12, CXCL14, their receptors, and other angiogenesis and immune cell infiltration and inflammatory factors as candidates for ERα-induced stroma-tumor signaling pathways. The results indicate that estrogen signaling in cervical cancer has dramatic differences from ERα+ breast cancers, and imply that estrogen signaling increasingly proceeds indirectly through ERα in tumor-associated stromal fibroblasts.
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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.