ArticleOncogene2005
Commutators of PAR-1 signaling in cancer cell invasion reveal an essential role of the Rho-Rho kinase axis and tumor microenvironment.
Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Expression of proteinase-activated receptor 1-4 (PAR 1-4) in human cancer.Journal of molecular histology · 2010Pooled it
- RhoA downregulation in the murine intestinal epithelium results in chronic Wnt activation and increased tumorigenesis.iScience · 2024Article
- Doxycycline Inhibits Cancer Stem Cell-Like PropertiesFrontiers in oncology · 2020Article
- Review
- Proteinase-activated receptors (PARs) - focus on receptor-receptor-interactions and their physiological and pathophysiological impact.Cell communication and signaling : CCS · 2013Review
- Development and maintenance of cancer stem cells under chronic inflammation.Journal of Nippon Medical School = Nippon Ika Daigaku zasshi · 2011Review
- Oxidative stress promotes myofibroblast differentiation and tumour spreading.EMBO molecular medicine · 2010Article
- Identification of key genes for carcinogenic pathways associated with colorectal adenoma-to-carcinoma progression.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2010Article
- Advantages of the AMDL-ELISA DR-70 (FDP) assay over carcinoembryonic antigen (CEA) for monitoring colorectal cancer patients.Journal of immunoassay & immunochemistry · 2010Article
- Molecular and pathological signatures of epithelial-mesenchymal transitions at the cancer invasion front.Histochemistry and cell biology · 2008Review
- Autocrine induction of invasion and metastasis by tumor-associated trypsin inhibitor in human colon cancer cells.Oncogene · 2008Review
- Gastrointestinal roles for proteinase-activated receptors in health and disease.British journal of pharmacology · 2008Review
- The influence of different microenvironments on melanoma invasiveness and microcirculation patterns: an animal experiment study in the mouse model.Journal of cancer research and clinical oncology · 2007Article
- Opposing roles of netrin-1 and the dependence receptor DCC in cancer cell invasion, tumor growth and metastasis.Oncogene · 2007Article
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 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We recently reported that proteinase-activated receptors type I (PAR-1) are coupled to both negative and positive invasion pathways in colonic and kidney cancer cells cultured on collagen type I gels. Here, we found that treatments with the cell-permeant analog 8-Br-cGMP and the soluble guanylate cyclase activator BAY41-2272, and Rho kinase (ROK) inhibition by Y27632 or a dominant negative form of ROK lead to PAR-1-mediated invasion through differential Rac1 and Cdc42 signaling. Hypoxia or the counteradhesive matricellular protein SPARC/BM-40 (SPARC: secreted protein acidic rich in cysteine) overexpressed during cancer progression also commutated PAR-1 to cellular invasion through the cGMP/protein kinase G (PKG) cascade, RhoA inactivation, and Rac1-dependent or -independent signaling. Cultured primary cancer cells isolated from peritoneal and pleural effusions from patients with colon cancer or other malignant tumors harbored PAR-1, as shown by RT-PCR and FACS analyses. These malignant effusions also contained high levels of activated thrombin and fibrin, and induced a proinvasive response in HCT8/S11 human colorectal cancer cells. Our data underline the essential role of the tumor microenvironment and of several commutators targeting cGMP/PKG signaling and the RhoA-ROK axis in the control of PAR-1 proinvasive activity and metastatic potential of cancer cells in distant organs and peritoneal or pleural cavities. We also add new insights into the mechanisms linking the coagulation mediators thrombin and PAR-1 in the context of blood coagulation disorders and venous thrombosis often observed in cancer patients, as described in 1865 by Armand Trousseau.
Indexed as
Identifiers
What OpenQuestion holds
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.