ArticleBritish journal of cancer2010
Enzastaurin inhibits invasion and metastasis in lung cancer by diverse molecules.
Article in British journal of cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.
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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
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2015Pooled it
- Guideline
- Phase 2 randomized study of enzastaurin (LY317615) for lung cancer prevention in former smokers.Cancer · 2013Trial
- Epithelial-to-mesenchymal transition (EMT) and cancer metastasis: the status quo of methods and experimental models 2025.Molecular cancer · 2025Review
- RFX2 downregulates RASSF1 expression and YAP phosphorylation through Hippo signaling to promote immune escape in lung adenocarcinoma.Cell division · 2025Article
- FHIT, a Novel Modifier Gene in Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2019Article
- Article
- Novel link between prostaglandin E2 (PGE2) and cholinergic signaling in lung cancer: The role of c-Jun in PGE2-induced α7 nicotinic acetylcholine receptor expression and tumor cell proliferation.Thoracic cancer · 2015Article
- Lipid-soluble ginseng extract inhibits invasion and metastasis of B16F10 melanoma cells.Journal of medicinal food · 2015Article
- Enzastaurin has anti-tumour effects in lung cancers with overexpressed JAK pathway molecules.British journal of cancer · 2012Article
- Drug repositioning in pulmonary arterial hypertension: challenges and opportunities.Pulmonary circulationArticle
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEnzastaurin (Enz) is a serine/threonine kinase inhibitor blocking protein kinase C (PKC)beta/AKT pathway. However, an ability of this compound to inhibit cancer invasion and metastasis is not yet clearly elucidated.
methodsThe ability of Enz to inhibit invasion and metastasis, and to target molecules was investigated in non-small cell lung cancer (NSCLC) by RT-PCR validated microarray, Matrigel, and in vivo chorionallantoic membrane (CAM) assays.
resultsEnzastaurin significantly reduced migration, invasion, and in vivo metastasis to lungs and liver (CAM assay) of diverse NSCLC cell lines. Genes promoting cancer progression (u-PAR, VEGFC, and HIF1alpha) and tumour suppression (VHL, RASSF1, and FHIT) of NSCLC were significantly (P<0.05) down- or upregulated after Enz treatment in H460, A549, and H1299 cells, respectively. Luciferase/chromatin immunoprecipitation analysis showed that Enz transcriptionally controls urokinase-type plasminogen activator receptor (u-PAR) expression by promoter inhibition through Sp1, Sp3, and c-Jun(AP-1). Moreover, siRNA knockdown of u-PAR re-sensitised Enz-resistant cells and induced apoptosis, suggesting u-PAR as a marker of Enz resistance.
conclusionThis study shows that Enz inhibits migration, invasion, and in vivo metastasis by targeting u-PAR, besides further targeting progression-related and tumour-suppressor genes in NSCLC. Together with u-PAR being a novel putative marker of Enz response, these data encourage molecularly tailored clinical studies on Enz in NSCLC therapy.
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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.