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PXD054180

PXD054180 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLapatinib-Induced Enhancement Of Mitochondrial Respiration In HER2-Positive SK-BR-3 Cells: Mechanism Revealed By Analysis Of Proteomic But Not Transcriptomic Data
DescriptionDual inhibitors of HER2 and EGFR, such as lapatinib, have shown significant efficacy for the therapy of HER2-positive breast cancer. Previous experiments showed that in cell cultures, the efficacy of lapatinib was significantly reduced by exposure to human serum and human epidermal growth factor (EGF). At the proteomic and transcriptomic levels, we examined the changes in the HER2-positive breast cancer cell line SK-BR-3 profiles upon treatment with lapatinib, either alone or in combination with human serum or EGF. Proteomic profiling revealed 350 differentially expressed proteins (DEPs) in response to lapatinib treatment at concentrations that induced cell growth arrest. Addition of human serum or EGF in combination with lapatinib prevented cell growth inhibition, and this combination treatment returned the expression of ~93% of DEPs to drug-free levels for both human serum and EGF. Gene ontology enrichment and OncoboxPD pathway activation level analysis showed that lapatinib addition influenced mostly common functional processes revealed in RNA- and protein-based assays. However, a specific feature was observed at the proteome level: addition of lapatinib increased the expression of proteins associated with mitochondrial function and cellular respiration. This feature was not observed when using RNA sequencing data for the same experiments. However, it is consistent with the results of the resazurin test, which showed a 1.8-fold increase in SK-BR-3 cellular respiration upon exposure to lapatinib. Thus, we conclude that enhanced cellular respiration is a novel additional mechanism of action of lapatinib on HER2-positive cancer cells.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:59:43.268.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAlexander Modestov
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-24 06:37:24ID requested
12024-09-26 10:05:09announced
22024-10-22 06:59:43announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: proteomics, squamous cell carcinoma SK-BR-3,HER-targeted cancer therapy, drug resistance, tricarboxylic acid cycle TCA, human blood serum, cellular respiration, lapatinib
Contact List
Dmitri Kamashev
contact affiliationShemyakin-Ovchinnikov Institute of Bioorganic Chemistry
contact emaildkamashev@gmail.com
lab head
Alexander Modestov
contact affiliationI.M. Sechenov First Moscow State Medical University
contact emailmodestov_a_a@staff.sechenov.ru
dataset submitter
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Dataset FTP location
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