ArticleBMC cancer2011
A functional and transcriptomic analysis of NET1 bioactivity in gastric cancer.
Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 32 citations in OpenAlex.
- Long-Read Single-Cell RNA Sequencing Reveals Dynamic Isoform Changes During Corneal Epithelial Wound Healing in Cynomolgus Monkeys.Investigative ophthalmology & visual science · 2026Article
- Conditional Overexpression of Net1 Enhances the Trans-Differentiation of Lgr5Cell proliferation · 2025Article
- NET1 is a critical regulator of spindle assembly and actin dynamics in mouse oocytes.Reproductive biology and endocrinology : RB&E · 2024Article
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- Article
- RHOA in Gastric Cancer: Functional Roles and Therapeutic Potential.Frontiers in genetics · 2019Review
- Stress-activated MAPKs and CRM1 regulate the subcellular localization of Net1A to control cell motility and invasion.Journal of cell science · 2018Article
- Regulation of autotaxin expression and secretion by lysophosphatidate and sphingosine 1-phosphate.Journal of lipid research · 2015Article
- A functional and protein-protein interaction analysis of neuroepithelial cell transforming gene 1 in hepatocellular carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Matricellular protein Cyr61 bridges lysophosphatidic acid and integrin pathways leading to cell migration.The Journal of biological chemistry · 2014Article
- Overexpression of GEFT, a Rho family guanine nucleotide exchange factor, predicts poor prognosis in patients with rhabdomyosarcoma.International journal of clinical and experimental pathology · 2014Article
- Expression of neuroepithelial transforming gene 1 is enhanced in oesophageal cancer and mediates an invasive tumour cell phenotype.Journal of experimental & clinical cancer research : CR · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNET1, a RhoA guanine exchange factor, is up-regulated in gastric cancer (GC) tissue and drives the invasive phenotype of this disease. In this study, we aimed to determine the role of NET1 in GC by monitoring the proliferation, motility and invasion of GC cells in which NET1 has been stably knocked down. Additionally, we aimed to determine NET1-dependent transcriptomic events that occur in GC.
methodsAn in vitro model of stable knockdown of NET1 was achieved in AGS human gastric adenocarcinoma cells via lentiviral mediated transduction of short-hairpin (sh) RNA targeting NET1. Knockdown was assessed using quantitative PCR. Cell proliferation was assessed using an MTS assay and cell migration was assessed using a wound healing scratch assay. Cell invasion was assessed using a transwell matrigel invasion assay. Gene expression profiles were examined using affymetrix oligonucleotide U133A expression arrays. A student's t test was used to determine changes of statistical significance.
resultsGC cells were transduced with NET1 shRNA resulting in a 97% reduction in NET1 mRNA (p < 0.0001). NET1 knockdown significantly reduced the invasion and migration of GC cells by 94% (p < 0.05) and 24% (p < 0.001) respectively, while cell proliferation was not significantly altered following NET1 knockdown. Microarray analysis was performed on non-target and knockdown cell lines, treated with and without 10 μM lysophosphatidic acid (LPA) allowing us to identify NET1-dependent, LPA-dependent and NET1-mediated LPA-induced gene transcription. Differential gene expression was confirmed by quantitative PCR. Shortlisted NET1-dependent genes included STAT1, TSPAN1, TGFBi and CCL5 all of which were downregulatd upon NET1 downregulation. Shortlisted LPA-dependent genes included EGFR and PPARD where EGFR was upregulated and PPARD was downregulated upon LPA stimulation. Shortlisted NET1 and LPA dependent genes included IGFR1 and PIP5K3. These LPA induced genes were downregulated in NET1 knockdown cells.
conclusionsNET1 plays an important role in GC cell migration and invasion, key aspects of GC progression. Furthermore, the gene expression profile further elucidates the molecular mechanisms underpinning NET1-mediated aggressive GC cell behaviour.
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