PXD049964 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Pharmacological Induction of the Hypoxia Response Pathway in Huh7 Hepatoma Cells with Molidustat |
Description | The hypoxia response pathway enables adaptation to oxygen deprivation. It is mediated by hypoxia-inducible factors (HIF), which promote metabolic reprogramming, erythropoiesis, angiogenesis and tissue remodeling. This has led to the successful development of HIF-inducing drugs for treating anemia and some of these molecules have now reached the market. However, and because high levels of HIFs are frequently associated to tumor growth, poor prognosis and drug resistance in different types of cancer and in particular hepatocellular carcinoma (HCC), there is concerns that HIF-inducing drugs could promote cancer development. We therefore analyzed in detail the effects of the HIF-inducing drug Molidustat on Huh7 cells, a well-characterized HCC cell line. Combined transcriptomics, proteomics, metabolomics showed that Molidustat reduced cell proliferation, increased the expression of glycolytic enzymes and fragmented the mitochondrial network while decreasing cellular respiration. This profound metabolic remodeling was associated with an improved usage of pyruvate to overcome the inhibition of mitochondrial respiration, and a reduced dependence of this organelle on pyrimidine supply. Overall, this study shows that Molidustat increases the metabolic plasticity of Huh7 cells to adapt changes in their microenvironment, arguing for careful monitoring of patients treated with HIF-inducing drugs when at risk of HCC. |
HostingRepository | PRIDE |
AnnounceDate | 2024-07-30 |
AnnouncementXML | Submission_2024-07-30_05:43:10.359.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Laure Perrin-Cocon |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-02-20 07:44:13 | ID requested | |
⏵ 1 | 2024-07-30 05:43:10 | announced | |
2 | 2024-10-22 06:51:47 | announced | 2024-10-22: Updated project metadata. |
Publication List
Keyword List
submitter keyword: HIF-1a, Molidustat, Hepatocellular carcinoma,Hypoxia |
Contact List
Pierre-Olivier Vidalain |
contact affiliation | CIRI, Centre International de Recherche en Infectiologie, Team Viral Infection, Metabolism and Immunity, Univ Lyon, Inserm, U1111, CNRS, UMR5308, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, 69007, Lyon, France |
contact email | pierre-olivier.vidalain@inserm.fr |
lab head | |
Laure Perrin-Cocon |
contact affiliation | CIRI - VIRIMI team |
contact email | laure.perrin@inserm.fr |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD049964
- Label: PRIDE project
- Name: Pharmacological Induction of the Hypoxia Response Pathway in Huh7 Hepatoma Cells with Molidustat