PXD049964-1

PXD049964 is an original dataset announced via ProteomeXchange.

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

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.

10.1007/S00018-024-05361-6;

submitter keyword: HIF-1a, Molidustat, Hepatocellular carcinoma,Hypoxia

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/07/PXD049964

PRIDE project URI

• PRIDE
  1. PXD049964
     1. Label: PRIDE project
     2. Name: Pharmacological Induction of the Hypoxia Response Pathway in Huh7 Hepatoma Cells with Molidustat