Rewiring Lipid Metabolism by Targeting PCSK9 and HMGCR to Treat Liver Cancer
| dc.rights.license | open | en_US |
| hal.structure.identifier | BoRdeaux Institute in onCology [Inserm U1312 - BRIC] | |
| dc.contributor.author | ALANNAN, Malak | |
| hal.structure.identifier | BoRdeaux Institute in onCology [Inserm U1312 - BRIC] | |
| dc.contributor.author | TRÉZÉGUET, Véronique | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| hal.structure.identifier | Cellomet [CHU Pellegrin, Bordeaux] | |
| dc.contributor.author | AMOÊDO, Nivea Dias | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| hal.structure.identifier | Cellomet [CHU Pellegrin, Bordeaux] | |
| dc.contributor.author | ROSSIGNOL, Rodrigue | |
| hal.structure.identifier | BoRdeaux Institute in onCology [Inserm U1312 - BRIC] | |
| dc.contributor.author | MAHFOUF, Walid | |
| hal.structure.identifier | BoRdeaux Institute in onCology [Inserm U1312 - BRIC] | |
| dc.contributor.author | REZVANI, Hamid Reza | |
| hal.structure.identifier | Laboratoire de biogenèse membranaire [LBM] | |
| dc.contributor.author | DITTRICH-DOMERGUE, Franziska | |
| hal.structure.identifier | Laboratoire de biogenèse membranaire [LBM] | |
| dc.contributor.author | MOREAU, Patrick
IDREF: 058610723 | |
| hal.structure.identifier | Bordeaux Imaging Center [BIC] | |
| dc.contributor.author | LACOMME, Sabrina | |
| hal.structure.identifier | Bordeaux Imaging Center [BIC] | |
| dc.contributor.author | GONTIER, Etienne | |
| hal.structure.identifier | BoRdeaux Institute in onCology [Inserm U1312 - BRIC] | |
| dc.contributor.author | GROSSET, Christophe | |
| hal.structure.identifier | الجامعة اللبنانية [بيروت] = Lebanese University [Beirut] = Université libanaise [Beyrouth] [LU / ULB] | |
| dc.contributor.author | BADRAN, Bassam | |
| hal.structure.identifier | الجامعة اللبنانية [بيروت] = Lebanese University [Beirut] = Université libanaise [Beyrouth] [LU / ULB] | |
| dc.contributor.author | FAYYAD-KAZAN, Hussein | |
| hal.structure.identifier | BoRdeaux Institute in onCology [Inserm U1312 - BRIC] | |
| dc.contributor.author | MERCHED, Aksam | |
| dc.date.accessioned | 2024-05-10T08:19:15Z | |
| dc.date.available | 2024-05-10T08:19:15Z | |
| dc.date.issued | 2023-01 | |
| dc.identifier.issn | 2072-6694 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/199733 | |
| dc.description.abstractEn | Alterations in lipid handling are an important hallmark in cancer. Our aim here is to target key metabolic enzymes to reshape the oncogenic lipid metabolism triggering irreversible cell breakdown. We targeted the key metabolic player proprotein convertase subtilisin/kexin type 9 (PCSK9) using a pharmacological inhibitor (R-IMPP) alone or in combination with 3-hydroxy 3-methylglutaryl-Coenzyme A reductase (HMGCR) inhibitor, simvastatin. We assessed the effect of these treatments using 3 hepatoma cell lines, Huh6, Huh7 and HepG2 and a tumor xenograft in chicken choriorallantoic membrane (CAM) model. PCSK9 deficiency led to dose-dependent inhibition of cell proliferation in all cell lines and a decrease in cell migration. Co-treatment with simvastatin presented synergetic anti-proliferative effects. At the metabolic level, mitochondrial respiration assays as well as the assessment of glucose and glutamine consumption showed higher metabolic adaptability and surge in the absence of PCSK9. Enhanced lipid uptake and biogenesis led to excessive accumulation of intracellular lipid droplets as revealed by electron microscopy and metabolic tracing. Using xenograft experiments in CAM model, we further demonstrated the effect of anti-PCSK9 treatment in reducing tumor aggressiveness. Targeting PCSK9 alone or in combination with statins deserves to be considered as a new therapeutic option in liver cancer clinical applications. | |
| dc.language.iso | EN | en_US |
| dc.subject.en | hepatocellular carcinoma | |
| dc.subject.en | hepatoblastoma | |
| dc.subject.en | lipotoxicity | |
| dc.subject.en | peridroplet mitochondria | |
| dc.title.en | Rewiring Lipid Metabolism by Targeting PCSK9 and HMGCR to Treat Liver Cancer | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.3390/cancers15010003 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio] | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hépatologie et Gastroentérologie | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Cancer | en_US |
| bordeaux.journal | Cancers | en_US |
| bordeaux.page | 3 | en_US |
| bordeaux.volume | 15 | en_US |
| bordeaux.hal.laboratories | Laboratoire de Biogenèse Membranaire (LBM) - UMR 5200 | en_US |
| bordeaux.issue | 1 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.import.source | hal | |
| hal.identifier | inserm-03920600 | |
| hal.version | 1 | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| workflow.import.source | hal | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Cancers&rft.date=2023-01&rft.volume=15&rft.issue=1&rft.spage=3&rft.epage=3&rft.eissn=2072-6694&rft.issn=2072-6694&rft.au=ALANNAN,%20Malak&TR%C3%89Z%C3%89GUET,%20V%C3%A9ronique&AMO%C3%8ADO,%20Nivea%20Dias&ROSSIGNOL,%20Rodrigue&MAHFOUF,%20Walid&rft.genre=article |
