dc.creator | Triantafyllou E.-A., Georgatsou E., Mylonis I., Simos G., Paraskeva E. | en |
dc.date.accessioned | 2023-01-31T10:09:53Z | |
dc.date.available | 2023-01-31T10:09:53Z | |
dc.date.issued | 2018 | |
dc.identifier | 10.1016/j.bbalip.2018.06.015 | |
dc.identifier.issn | 13881981 | |
dc.identifier.uri | http://hdl.handle.net/11615/79773 | |
dc.description.abstract | Hypoxia inducible factor-1 (HIF-1) supports survival of normal cells under low oxygen concentration and cancer cells in the hypoxic tumor microenvironment. This involves metabolic reprogramming via upregulation of glycolysis, downregulation of oxidative phosphorylation and, less well documented, effects on lipid metabolism. To investigate the latter, we examined expression of relevant enzymes in cancer cells grown under hypoxia. We show that expression of acylglycerol-3-phosphate acyltransferase 2 (AGPAT2), also known as lysophosphatidic acid acyltransferase β (LPAATβ), was upregulated under hypoxia and this was impaired by siRNA-mediated knockdown of HIF-1α. Moreover, a sequence of the AGPAT2 gene promoter region, containing 6 putative Hypoxia Response Elements (HREs), activated transcription of a reporter gene under hypoxic conditions or in normoxic cells over-expressing HIF-1α. Chromatin immunoprecipitation experiments confirmed binding of HIF-1α to one of these HREs, mutation of which abolished hypoxic activation of the AGPAT2 promoter. Knockdown of AGPAT2 by siRNA reduced lipid droplet accumulation and cell viability under hypoxia and increased cancer cell sensitivity to the chemotherapeutic etoposide. In conclusion, our findings demonstrate that AGPAT2, which is mutated in patients with congenital generalized lipodystrophy and over-expressed in different types of cancer, is a direct transcriptional target of HIF-1, suggesting that upregulation of lipid storage by HIF-1 plays an important role in adaptation and survival of cancer cells under low oxygen conditions. © 2018 Elsevier B.V. | en |
dc.language.iso | en | en |
dc.source | Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85049060634&doi=10.1016%2fj.bbalip.2018.06.015&partnerID=40&md5=b90e28d175323127d2a0513def4459d6 | |
dc.subject | acylglycerol 3 phosphate acyltransferase 2 | en |
dc.subject | acyltransferase | en |
dc.subject | etoposide | en |
dc.subject | fat droplet | en |
dc.subject | glycerophospholipid | en |
dc.subject | hypoxia inducible factor 1 | en |
dc.subject | small interfering RNA | en |
dc.subject | triacylglycerol | en |
dc.subject | unclassified drug | en |
dc.subject | 1 acylglycerophosphate acyltransferase | en |
dc.subject | 2-acylglycerophosphate acyltransferase | en |
dc.subject | acyltransferase | en |
dc.subject | AGPAT1 protein, human | en |
dc.subject | antineoplastic agent | en |
dc.subject | etoposide | en |
dc.subject | fat droplet | en |
dc.subject | glycerophospholipid | en |
dc.subject | HIF1A protein, human | en |
dc.subject | hypoxia inducible factor 1alpha | en |
dc.subject | protein binding | en |
dc.subject | small interfering RNA | en |
dc.subject | triacylglycerol | en |
dc.subject | Article | en |
dc.subject | cancer resistance | en |
dc.subject | cell survival | en |
dc.subject | cell viability | en |
dc.subject | chromatin immunoprecipitation | en |
dc.subject | controlled study | en |
dc.subject | enzyme induction | en |
dc.subject | female | en |
dc.subject | gene sequence | en |
dc.subject | HeLa cell line | en |
dc.subject | Huh-7 cell line | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | hypoxia | en |
dc.subject | lipid metabolism | en |
dc.subject | liver cell carcinoma | en |
dc.subject | oxidative phosphorylation | en |
dc.subject | priority journal | en |
dc.subject | promoter region | en |
dc.subject | protein expression | en |
dc.subject | protein synthesis | en |
dc.subject | regulatory mechanism | en |
dc.subject | reporter gene | en |
dc.subject | site directed mutagenesis | en |
dc.subject | upregulation | en |
dc.subject | Western blotting | en |
dc.subject | antagonists and inhibitors | en |
dc.subject | biosynthesis | en |
dc.subject | cell hypoxia | en |
dc.subject | cell survival | en |
dc.subject | DNA responsive element | en |
dc.subject | drug effect | en |
dc.subject | drug resistance | en |
dc.subject | gene expression regulation | en |
dc.subject | genetics | en |
dc.subject | HEK293 cell line | en |
dc.subject | liver cell | en |
dc.subject | metabolism | en |
dc.subject | mutation | en |
dc.subject | pathology | en |
dc.subject | signal transduction | en |
dc.subject | transcription initiation | en |
dc.subject | tumor cell line | en |
dc.subject | 1-Acylglycerol-3-Phosphate O-Acyltransferase | en |
dc.subject | Acyltransferases | en |
dc.subject | Antineoplastic Agents, Phytogenic | en |
dc.subject | Cell Hypoxia | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Cell Survival | en |
dc.subject | Drug Resistance, Neoplasm | en |
dc.subject | Etoposide | en |
dc.subject | Gene Expression Regulation, Neoplastic | en |
dc.subject | Glycerophospholipids | en |
dc.subject | HEK293 Cells | en |
dc.subject | HeLa Cells | en |
dc.subject | Hepatocytes | en |
dc.subject | Humans | en |
dc.subject | Hypoxia-Inducible Factor 1, alpha Subunit | en |
dc.subject | Lipid Droplets | en |
dc.subject | Lipid Metabolism | en |
dc.subject | Mutation | en |
dc.subject | Promoter Regions, Genetic | en |
dc.subject | Protein Binding | en |
dc.subject | Response Elements | en |
dc.subject | RNA, Small Interfering | en |
dc.subject | Signal Transduction | en |
dc.subject | Transcriptional Activation | en |
dc.subject | Triglycerides | en |
dc.subject | Elsevier B.V. | en |
dc.title | Expression of AGPAT2, an enzyme involved in the glycerophospholipid/triacylglycerol biosynthesis pathway, is directly regulated by HIF-1 and promotes survival and etoposide resistance of cancer cells under hypoxia | en |
dc.type | journalArticle | en |