PXD012043

PXD012043 is an original dataset announced via ProteomeXchange.

Title	Total protein profiles of human induced pluripotent stem cell-derived cardiomyocytes in response to four tyrosine kinase inhibitors
Description	Drug-induced cardiotoxicity is a widespread clinical issue affecting numerous drug classes and remains difficult to treat. One such drug class is Tyrosine Kinase Inhibitors (TKIs), which cause varying degrees of contraction-related cardiotoxicity usually after weeks of exposure. Understanding molecular mechanisms underlying both acute and chronic toxicity of TKIs could help identify new treatment opportunities. Here, we presented transcriptome responses to four TKIs (Sunitinib, Sorafenib, Lapatinib and Erlotinib) across 3 doses and 4 time points in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Gene expression evolved continually under drug treatment and revealed changes in several biological networks that were associated with cardiac metabolism and contraction. These changes were confirmed by proteomics and resulted in metabolic and structural remodeling of hiPSC-CMs. One of the metabolic remodeling was the increased aerobic glycolysis induced by Sorafenib, which is an adaptive response in preserving cell survival under Sorafenib treatment. Drug adaptation in cardiac cells may represent new targets for managing chronic forms of TKI-induced cardiotoxicity.
HostingRepository	PRIDE
AnnounceDate	2019-06-03
AnnouncementXML	Submission_2019-06-03_07:56:05.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthew Berberich
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-13 01:43:42	ID requested
1	2019-05-16 02:47:49	announced
⏵ 2	2019-06-03 07:56:07	announced	Updated project metadata.

Wang H, Sheehan RP, Palmer AC, Everley RA, Boswell SA, Ron-Harel N, Ringel AE, Holton KM, Jacobson CA, Erickson AR, Maliszewski L, Haigis MC, Sorger PK, Adaptation of Human iPSC-Derived Cardiomyocytes to Tyrosine Kinase Inhibitors Reduces Acute Cardiotoxicity via Metabolic Reprogramming. Cell Syst, 8(5):412-426.e7(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: drug adaptation, tyrosine kinase inhibitor, human induced pluripotent stem cell-derived cardiomyocyte, cardiotoxicity, aerobic glycolysis, mitochondrial respiration, Tandem Mass Tag Mass Spectrometry

Peter K. Sorger
contact affiliation	Otto Krayer Professor Department of Systems Biology Head of the Harvard Program in Therapeutic Sciences Harvard Medical School 200 Longwood Avenue, WAB440 Boston, MA 02115
contact email	peter_sorger@hms.harvard.edu
lab head
Matthew Berberich
contact affiliation	Harvard Program In Therapeutic Science/Harvard Medical School
contact email	matthew_berberich@hms.harvard.edu
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/2019/05/PXD012043

PRIDE project URI

• PRIDE
  1. PXD012043
     1. Label: PRIDE project
     2. Name: Total protein profiles of human induced pluripotent stem cell-derived cardiomyocytes in response to four tyrosine kinase inhibitors