Autotaxin (ATX) or Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2) is a secreted enzyme with lysophospholipase D activity, with its primary function being the extracellular hydrolysis of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a bioactive lipid [...].
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| http://dx.doi.org/10.3390/ijms24098325 | DOI Listing |
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Reduced Oxidative Susceptibility of Lp(a) and LDL Fractions as a Pleiotropic Effect of Lipoprotein Apheresis in Patients with Elevated Lp(a) and ASCVDs.
Int J Mol Sci
December 2024
Department of Clinical Chemistry, Medical University of Gdańsk, 80-211 Gdańsk, Poland.
Oxidative modifications of lipoproteins play a crucial role in the initiation of atherosclerotic cardiovascular diseases (ASCVDs). Nowadays, the one effective strategy for the treatment of patients with hyperlipoproteinemia(a) is lipoprotein apheresis (LA), which has a pleiotropic effect on reducing the risk of ASCVDs. The significance of oxidative susceptibility of the LDL fraction in ASCVDs has been extensively studied.
View Article and Find Full Text PDFDiscovery of Novel 4,5,6,7-Tetrahydro-7-pyrazolo[3,4-]pyridin-7-one Derivatives as Orally Efficacious ATX Allosteric Inhibitors for the Treatment of Pulmonary Fibrosis.
J Med Chem
January 2025
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Pulmonary fibrosis (PF) is a progressive, fatal lung disease lacking effective treatments. Autotaxin (ATX) plays a crucial role in exacerbating inflammation and fibrosis, making it a promising target for fibrosis therapies. Herein, starting from PAT-409 (Cudetaxestat), a series of novel ATX inhibitors bearing 1-indole-3-carboxamide, 4,5,6,7-tetrahydro-7-pyrazolo[3,4-]pyridin-7-one, or 4,5,6,7-tetrahydro-1-pyrazolo[4,3-]pyridine cores were designed based on the structure of ATX hydrophobic tunnel.
View Article and Find Full Text PDFPancreatic CAF-derived Autotaxin (ATX) drives autocrine CTGF expression to modulate pro-tumorigenic signaling.
Mol Cancer Ther
November 2024
Cancer Research Horizons, Cambridge, United Kingdom.
Autotaxin (ATX), encoded by ENPP2, is a clinical target in pancreatic ductal adenocarcinoma (PDAC). ATX catalyzes the production of lysophosphatidic acid (LPA), an important regulator within the tumor microenvironment (TME), yet the pro-tumorigenic action of the ATX/LPA axis in PDAC remains unclear. Here, by interrogating patient samples and cell line datasets, we show that the PDAC TME, rather than cancer cells, is responsible for the majority of ENPP2 expression, and highlight a key role for cancer associated fibroblast (CAF)-derived ATX in autocrine and paracrine pro-tumorigenic signaling.
View Article and Find Full Text PDFHigh levels of autotaxin and lysophosphatidic acid predict poor outcome in treatment of resectable gastric carcinoma.
Eur J Cancer
December 2024
Scientific Direction, National Institute of Gastroenterology, IRCCS "S. de Bellis" Research Hospital, 70013 Castellana Grotte, BA, Italy. Electronic address:
Article Synopsis
- Early-stage gastric cancer often goes undetected due to a lack of specific symptoms, resulting in late diagnoses and advanced disease, highlighting the need for new biomarkers for early detection and treatment matching.
- The study investigated the prognostic significance of ENPP2/Autotaxin (ATX) and lysophosphatidic acid (LPA) in Gastro-Esophageal Adenocarcinoma (GEA), finding that higher levels of these substances could indicate worse patient outcomes.
- Results showed that while ENPP2 mutations are infrequent, they are linked to lower overall survival, and surgical removal of tumors significantly reduced serum ATX and LPA levels, suggesting potential for targeted therapies based on these biomarkers in future clinical trials.
Bronchopulmonary dysplasia demonstrates dysregulated autotaxin/lysophosphatidic acid signaling in a neonatal mouse model.
Pediatr Res
October 2024
Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease affecting premature infants who require oxygen supplementation and ventilator therapy to support their underdeveloped lungs. Autotaxin (ATX), an enzyme that generates the bioactive phospholipid lysophosphatidic acid (LPA), which acts via G-protein coupled receptors, has been implicated in numerous pulmonary diseases. In this study, we explored the pathophysiological role of the ATX/LPA signaling pathway in BPD.
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