Hydroxycarboxylic acid receptors are essential for breast cancer cells to control their lipid/fatty acid metabolism
| Autor: | Oliver Jay Broom, Anders Nordström, Claudia Stäubert |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Time Factors
Perhexiline cancer metabolism Breast Neoplasms GPR81 Receptors Nicotinic Pharmacology Biology Transfection GPR109a Receptors G-Protein-Coupled chemistry.chemical_compound Breast cancer Tandem Mass Spectrometry Cell Line Tumor Tumor Cells Cultured medicine Humans RNA Messenger Enzyme Inhibitors Receptor Cell Proliferation Cancer och onkologi Carnitine O-Palmitoyltransferase Cell Death Fatty acid metabolism Fatty Acids Cancer Lipid metabolism Lipid Metabolism medicine.disease Gene Expression Regulation Neoplastic HEK293 Cells Oncology chemistry metabolite-sensing GPCRs Gene Knockdown Techniques Cancer and Oncology Cancer cell Epoxy Compounds Female RNA Interference Signal transduction Oxidation-Reduction Chromatography Liquid Signal Transduction Research Paper hydroxycarboxylic acid receptors |
| Zdroj: | Oncotarget |
| Popis: | // Claudia Staubert 1,2,3 , Oliver Jay Broom 2 and Anders Nordstrom 1,2 1 Swedish Metabolomics Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umea, Sweden 2 Department of Molecular Biology, Umea University, Umea, Sweden 3 Institute of Biochemistry, Faculty of Medicine, University of Leipzig, Leipzig, Germany Correspondence to: Claudia Staubert, email: // Anders Nordstrom, email: // Keywords : hydroxycarboxylic acid receptors, cancer metabolism, metabolite-sensing GPCRs, GPR81, GPR109a Received : August 28, 2014 Accepted : February 26, 2015 Published : March 14, 2015 Abstract Cancer cells exhibit characteristic changes in their metabolism with efforts being made to address them therapeutically. However, targeting metabolic enzymes as such is a major challenge due to their essentiality for normal proliferating cells. The most successful pharmaceutical targets are G protein-coupled receptors (GPCRs), with more than 40% of all currently available drugs acting through them. We show that, a family of metabolite-sensing GPCRs, the Hydroxycarboxylic acid receptor family (HCAs), is crucial for breast cancer cells to control their metabolism and proliferation. We found HCA 1 and HCA 3 mRNA expression were significantly increased in breast cancer patient samples and detectable in primary human breast cancer patient cells. Furthermore, siRNA mediated knock-down of HCA 3 induced considerable breast cancer cell death as did knock-down of HCA 1 , although to a lesser extent. Liquid Chromatography Mass Spectrometry based analyses of breast cancer cell medium revealed a role for HCA 3 in controlling intracellular lipid/fatty acid metabolism. The presence of etomoxir or perhexiline, both inhibitors of fatty acid β-oxidation rescues breast cancer cells with knocked-down HCA 3 from cell death. Our data encourages the development of drugs acting on cancer-specific metabolite-sensing GPCRs as novel anti-proliferative agents for cancer therapy. |
| Databáze: | OpenAIRE |
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