ArticlePloS one2009
Novel anti-metastatic action of cidofovir mediated by inhibition of E6/E7, CXCR4 and Rho/ROCK signaling in HPV tumor cells.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
25 citing papers in PubMed, 54 citations in OpenAlex.
- 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
- Research progress of ECT2 and RhoA-related signaling pathways in gynecological tumors.Frontiers in cell and developmental biology · 2025Review
- The Micro-Immunotherapy Medicine 2LPAPICancers · 2024Article
- Review
- The Role of Chemokines in Cervical Cancers.Medicina (Kaunas, Lithuania) · 2021Review
- Advances in Designing and Developing Vaccines, Drugs and Therapeutic Approaches to Counter Human Papilloma Virus.Frontiers in immunology · 2018Review
- DNA vaccine encoding human papillomavirus antigens flanked by a signal peptide and a KDEL sequence induces a potent therapeutic antitumor effect.Oncology letters · 2017Article
- Phase I trial evaluating the antiviral agent Cidofovir in combination with chemoradiation in cervical cancer patients.Oncotarget · 2016Article
- Review
- The broad-spectrum anti-DNA virus agent cidofovir inhibits lung metastasis of virus-independent, FGF2-driven tumors.Oncotarget · 2015Article
- HPV Carcinomas in Immunocompromised Patients.Journal of clinical medicine · 2015Review
- Rho/ROCK signaling in motility and metastasis of gastric cancer.World journal of gastroenterology · 2014Review
- CXCR4: a virus's best friend?Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2014Review
- The regulation of inflammatory pathways and infectious disease of the cervix by seminal fluid.Pathology research international · 2014Review
- Cidofovir selectivity is based on the different response of normal and cancer cells to DNA damage.BMC medical genomics · 2013Article
- ROCK1 & 2 perform overlapping and unique roles in angiogenesis and angiosarcoma tumor progression.Current molecular medicine · 2013Article
- Therapy of human papillomavirus-related disease.Vaccine · 2012Review
- Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells.BMC cancer · 2012Article
- Regulation of inflammatory pathways in cancer and infectious disease of the cervix.Scientifica · 2012Review
- Rho kinase proteins--pleiotropic modulators of cell survival and apoptosis.Anticancer research · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cervical cancer is frequently associated with HPV infection. The expression of E6 and E7 HPV oncoproteins is a key factor in its carcinogenicity and might also influence its virulence, including metastatic conversion. The cellular mechanisms involved in metastatic spread remain elusive, but pro-adhesive receptors and their ligands, such as SDF-1alpha and CXCR4 are implicated. In the present study, we assessed the possible relationship between SDF-1alpha/CXCR4 signaling, E6/E7 status and the metastatic process. We found that SDF-1alpha stimulated the invasion of E6/E7-positive cancer cell lines (HeLa and TC-1) in Matrigel though CXCR4 and subsequent Rho/ROCK activation. In pulmonary metastatic foci generated by TC-1 cells IV injection a high proportion of cells expressed membrane-associated CXCR4. In both cases models (in vitro and in vivo) cell adhesion and invasion was abrogated by CXCR4 immunological blockade supporting a contribution of SDF-1alpha/CXCR4 to the metastatic process. E6 and E7 silencing using stable knock-down and the approved anti-viral agent, Cidofovir decreased CXCR4 gene expression as well as both, constitutive and SDF-1alpha-induced cell invasion. In addition, Cidofovir inhibited lung metastasis (both adhesion and invasion) supporting contribution of E6 and E7 oncoproteins to the metastatic process. Finally, potential signals activated downstream SDF-1alpha/CXCR4 and involved in lung homing of E6/E7-expressing tumor cells were investigated. The contribution of the Rho/ROCK pathway was suggested by the inhibitory effect triggered by Cidofovir and further confirmed using Y-27632 (a small molecule ROCK inhibitor). These data suggest a novel and highly translatable therapeutic approach to cervix cancer, by inhibition of adhesion and invasion of circulating HPV-positive tumor cells, using Cidofovir and/or ROCK inhibition.
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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.