ArticlePloS one2013
HPV16 oncoproteins promote cervical cancer invasiveness by upregulating specific matrix metalloproteinases.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Changes in the Extracellular Matrix in Endometrial and Cervical Cancer: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Prognostic Role of Matrix Metalloproteinases in Cervical Cancer: A Meta-Analysis.Cancer control : journal of the Moffitt Cancer CenterPooled it
- Causal Relationship Between Matrix Metalloproteinase and Cervical Lesions: A Two-Sample Mendelian Randomization Analysis.International journal of women's health · 2025Article
- Structure and transcription of integrated HPV DNA in vulvar carcinomas.NPJ genomic medicine · 2024Article
- Multidimensional outlook on the pathophysiology of cervical cancer invasion and metastasis.Molecular and cellular biochemistry · 2023Review
- Molecular Mechanisms Driven by MT4-MMP in Cancer Progression.International journal of molecular sciences · 2023Review
- Tumor microenvironment promotes lymphatic metastasis of cervical cancer: its mechanisms and clinical implications.Frontiers in oncology · 2023Review
- Expression of matrix metalloproteinases (MMPs)-2/-7/-9/-14 and tissue inhibitors of MMPs (TIMPs)-1/-2 in bovine cutaneous fibropapillomas associated with BPV-2 infection.Frontiers in veterinary science · 2022Article
- The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis.Viruses · 2021Review
- Article
- Telomerase Reverse Transcriptase (TERT) Expression, Telomerase Activity, and Expression of Matrix Metalloproteinases (MMP)-1/-2/-9 in Feline Oral Squamous Cell Carcinoma Cell Lines Associated WithFrontiers in veterinary science · 2020Article
- The HPV-18 E7 CKII phospho acceptor site is required for maintaining the transformed phenotype of cervical tumour-derived cells.PLoS pathogens · 2019Article
- 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
- MMP Secretion Rate and Inter-invadopodia Spacing Collectively Govern Cancer Invasiveness.Biophysical journal · 2018Article
- Matrix metalloproteinase-7 may serve as a novel biomarker for cervical cancer.OncoTargets and therapy · 2018Article
- Praeruptorin A Inhibits Human Cervical Cancer Cell Growth and Invasion by Suppressing MMP-2 Expression and ERK1/2 Signaling.International journal of molecular sciences · 2017Article
- Article
- Human Papillomavirus and the Stroma: Bidirectional Crosstalk during the Virus Life Cycle and Carcinogenesis.Viruses · 2017Review
- The human papillomavirus E7 oncoprotein as a regulator of transcription.Virus research · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Production of matrix metalloproteinases (MMPs) for degradation of extracellular matrix is a vital step in cancer metastasis. We investigated the effects of HPV16 oncoproteins (16E6, 16E6*I and 16E7), either individually or combined, on the transcription of 7 MMPs implicated in cervical cancer invasiveness. The levels of 7 MMPs reported to be increased in cervical cancer were determined in C33A stably expressing different HPV16 oncoproteins using quantitative RT-PCR and compared with invasion ability of cell lines using in vitro invasion and wound healing assays. Overexpression of MMP-2 and MT1-MMP was detected in HPV16E6E7 expressing cells which correlated with increased cell invasion. Combination of HPV oncoproteins always showed greater effects than its individual form. Inhibition of cell invasion using a specific MMP-2 inhibitor, OA-Hy, and anti-MT1-MMP antibody confirmed that invasion in these cells was dependent on both MMP-2 and MT1-MMP expression. Depletion of HPV16E6E7 by shRNA-mediated knock-down experiments resulted in decreased MMP-2 and MT1-MMP expression levels as well as reduced invasion ability which strongly suggested specific effects of HPV oncoproteins on both MMPs and on cell invasion. Immunohistochemistry study in invasive cervical cancers confirmed the enhanced in vivo expression of these two MMPs in HPV16-infected cells. In addition, possible sites required by HPV16E6E7 on the MMP-2 and MT1-MMP promoters were investigated and PEA3 (at -552/-540 for MMP-2, -303 for MT1-MMP) and Sp1 (at -91 for MMP-2, -102 for MT1-MMP) binding sites were shown to be essential for mediating their transactivation activity. In conclusion, our study demonstrated that HPV16E6 and E7 oncoproteins cooperate in promoting cervical cancer invasiveness by specifically upregulating MMP-2 and MT1-MMP transcription in a similar manner.
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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.