PXD054756

PXD054756 is an original dataset announced via ProteomeXchange.

Title	Diclofenac and acetaminophen dim the acute phase response but amplify expression of the iron regulator hepcidin in liver cancer cells - HepG2
Description	Cancer patients frequently suffer from anemia and cancer-related pain, which can be treated by non-opioid analgesics like Diclofenac (DCF) and Acetaminophen (APAP) attenuating inflammatory responses. The key pro-inflammatory cytokine interleukin (IL)-6 triggers expression of acute phase proteins, including the iron regulator hepcidin. We show by quantitative proteomics and dynamic pathway modelling that DCF and APAP enhance the induction of the feedback-inhibitor SOCS3 and reduce IL-6 mediated STAT3 phosphorylation in hepatoma cells. Consequently, expression of acute phase proteins is decreased with the exception of hepcidin. Our mathematical modelling approach reveals that due to an autocrine activation loop of BMP signaling hepcidin expression in hepatoma cells is amplified and this loop is absent in primary hepatocytes. We experimentally validate our model-based prediction that co-inhibition of the BMP receptor is most promising to reduce excessive hepcidin production in hepatoma cells and could be exploited to prevent iron deficiency caused anemia in liver cancer.
HostingRepository	PRIDE
AnnounceDate	2025-11-11
AnnouncementXML	Submission_2025-11-11_00:35:40.143.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcel Schilling
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-09 05:43:41	ID requested
⏵ 1	2025-11-11 00:35:40	announced

10.1016/J.CELS.2025.101431;

submitter keyword: Bone morphogenetic protein signaling,Liver cancer, Mathematical modeling,Anemia,Drug-induced liver injury,Hepcidin,Interleukin-6

Prof. Dr. Ursula Klingmüller
contact affiliation	German Cancer Research Center (DKFZ) Division Systems Biology of Signal Transduction Im Neuenheimer Feld 280 69120 Heidelberg Germany
contact email	u.klingmueller@dkfz.de
lab head
Marcel Schilling
contact affiliation	Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg
contact email	m.schilling@dkfz.de
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/2025/11/PXD054756

PRIDE project URI

• PRIDE
  1. PXD054756
     1. Label: PRIDE project
     2. Name: Diclofenac and acetaminophen dim the acute phase response but amplify expression of the iron regulator hepcidin in liver cancer cells - HepG2