ArticlePloS one2012
HPV16 oncoproteins induce MMPs/RECK-TIMP-2 imbalance in primary keratinocytes: possible implications in cervical carcinogenesis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Laryngeal squamous cell carcinoma: a functional "two-hit" model of papillomavirus-Epstein-Barr virus synergistic carcinogenesis.Frontiers in cellular and infection microbiology · 2026Pooled it
- The Roles of the Membrane-Anchored Glycoprotein RECK in Animal Development, Tumor Suppression, and Beyond.Life (Basel, Switzerland) · 2026Review
- Immunohistochemical and western blot expression of MMPs, TIMPs, and cytokeratin 10 in feline squamous cell carcinoma.Frontiers in veterinary science · 2026Article
- Roles of human papillomavirus in cancers: oncogenic mechanisms and clinical use.Signal transduction and targeted therapy · 2025Review
- HIV-1 Tat-induced disruption of epithelial junctions and epithelial-mesenchymal transition of oral and genital epithelial cells lead to increased invasiveness of neoplastic cells and the spread of herpes simplex virus and cytomegalovirus.Frontiers in immunology · 2025Review
- Article
- Field experience with the 8-HPV-type oncoprotein test for cervical cancer screening among HPV-positive women living with and without HIV in LMICs.International journal of cancer · 2024Article
- Structure and transcription of integrated HPV DNA in vulvar carcinomas.NPJ genomic medicine · 2024Article
- MiR-21 Regulates Growth and Migration of Cervical Cancer Cells by RECK Signaling Pathway.International journal of molecular sciences · 2024Article
- MiR-106b-5p Promotes Malignant Behaviors of Cervical Squamous Cell Carcinoma Cells by Targeting TIMP2.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Virus-associated disruption of mucosal epithelial tight junctions and its role in viral transmission and spread.Tissue barriers · 2021Review
- Article
- Insights Into the Regulation of Gynecological Inflammation-Mediated Malignancy by Metalloproteinases.Frontiers in cell and developmental biology · 2021Review
- Comprehensive gene and pathway analysis of cervical cancer progression.Oncology letters · 2020Article
- MicroRNA-130a regulated by HPV18 E6 promotes proliferation and invasion of cervical cancer cells by targeting TIMP2.Experimental and therapeutic medicine · 2019Article
- Glycoprotein nonmetastatic melanoma protein B accelerates tumorigenesis of cervical cancer in vitro by regulating the Wnt/β-catenin pathway.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2018Article
- Alterations in the expression and activity of extracellular matrix components in HPV-associated infections and diseases.Clinics (Sao Paulo, Brazil) · 2018Review
- The Impact of Human Papilloma Viruses, Matrix Metallo-Proteinases and HIV Protease Inhibitors on the Onset and Progression of Uterine Cervix Epithelial Tumors: A Review of Preclinical and Clinical Studies.International journal of molecular sciences · 2018Review
- Human papillomavirus E6-regulated microRNA-20b promotes invasion in cervical cancer by targeting tissue inhibitor of metalloproteinase 2.Molecular medicine reports · 2017Article
- Inhibition of MMP-9 expression by ritonavir or saquinavir is associated with inactivation of the AKT/Fra-1 pathway in cervical intraepithelial neoplasia cells.Oncology letters · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cervical cancer is the third most common cancer in women worldwide. Persistent infection with high-risk HPV types, principally HPV16 and 18 is the main risk factor for the development of this malignancy. However, the onset of invasive tumor occurs many years after initial exposure in a minority of infected women. This suggests that other factors beyond viral infection are necessary for tumor establishment and progression. Tumor progression is characterized by an increase in secretion and activation of matrix metalloproteinases (MMPs) produced by either the tumor cells themselves or tumor-associated fibroblasts or macrophages. Increased MMPs expression, including MMP-2, MMP-9 and MT1-MMP, has been observed during cervical carcinoma progression. These proteins have been associated with degradation of ECM components, tumor invasion, metastasis and recurrence. However, few studies have evaluated the interplay between HPV infection and the expression and activity of MMPs and their regulators in cervical cancer. We analyzed the effect of HPV16 oncoproteins on the expression and activity of MMP-2, MMP-9, MT1-MMP, and their inhibitors TIMP-2 and RECK in cultures of human keratinocytes. We observed that E7 expression is associated with increased pro-MMP-9 activity in the epithelial component of organotypic cultures, while E6 and E7 oncoproteins co-expression down-regulates RECK and TIMP-2 levels in organotypic and monolayers cultures. Finally, a study conducted in human cervical tissues showed a decrease in RECK expression levels in precancer and cancer lesions. Our results indicate that HPV oncoproteins promote MMPs/RECK-TIMP-2 imbalance which may be involved in HPV-associated lesions outcome.
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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.