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PXD036348

PXD036348 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTranscriptome and phosphoproteome analyses of gemcitabine-resistant gallbladder cancer cells provide novel insights into molecular changes occurring during acquired resistance
DescriptionTreatment options for advanced gallbladder cancer (GBC) are scarce and usually rely on cytotoxic chemotherapy, but unfortunately the effectiveness of any regimen is limited, and recurrence rates are high. Here, we established and characterized two gemcitabine-resistant GBC cell sublines (NOZ GemR and TGBC1 GemR) to investigate the molecular mechanisms associated with acquired resistance in vitro. The transcriptome profiling of parental and gemcitabine resistant cells revealed differential expression of multiple protein-coding genes and enrichment of biological processes such as epithelial-to-mesenchymal transition and drug metabolism. On the other hand, quantitative phosphotyrosine proteomic analysis of NOZ GemR identified aberrantly dysregulated signaling pathways in resistant cells as well as active kinases, such as Abl, PDGFRA, EphB2 and members of the Src-family that could be novel therapeutic targets against drug resistance in GBC. In line with this, NOZ GemR cells showed increased sensitivity toward the multikinase inhibitor dasatinib compared with parental cells. In conclusion, our study describes transcriptome changes and altered signaling pathways occurring in gemcitabine-resistant gallbladder cancer cells, which greatly expands our understanding of the underlying mechanisms of acquired drug-resistance in GBC. Moreover, this new gemcitabine resistant GBC models could be exploited either to study alternative mechanisms of resistance or to explore new therapies for chemotherapy-refractory GBC.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:45:27.655.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD036348
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJun Zhong
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-27 06:01:41ID requested
12023-05-03 08:12:47announced
22023-11-14 08:45:35announced2023-11-14: Updated project metadata.
Publication List
Vergara-G, ó, mez L, Bizama C, Zhong J, Buchegger K, Su, á, rez F, Rosa L, Ili C, Weber H, Obreque J, Espinoza K, Repetto G, Roa JC, Leal P, Garc, í, a P, A Novel Gemcitabine-Resistant Gallbladder Cancer Model Provides Insights into Molecular Changes Occurring during Acquired Resistance. Int J Mol Sci, 24(8):(2023) [pubmed]
10.6019/PXD036348;
Keyword List
submitter keyword: gemcitabine resistance,Gallbladder cancer
Contact List
Patricia García
contact affiliationDepartment of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, 8330024, Chile
contact emailpgarciam@uc.cl
lab head
Jun Zhong
contact affiliationDelta Omics Inc
contact emailjzhong@deltaomics.com
dataset submitter
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Dataset FTP location
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PRIDE project URI
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