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PXD044698

PXD044698 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCombined inhibition of MNK signaling and BET proteins reveals TGM2 as a novel vulnerability in melanoma
DescriptionMelanoma is the deadliest form of skin cancer. MAPK-targeted therapies (MAPKi) and immune checkpoint inhibitors (ICI) have shown clinical benefit but are limited by resistance mechanisms that remain poorly defined. MNK1/2 inhibitors (MNKi) have shown promising effects in pre-clinical tumor models, particularly in melanoma. Herein, we find that bromodomain and extra-terminal domain protein inhibitors (BETi) in combination with MNKi reduce the proliferation of melanoma cells, including cells with acquired MAPKi resistance. Transcriptomic and proteomic analyses reveal that tissue transglutaminase TGM2 and inhibition of FAK activation are downstream effectors of this combination. We further demonstrate that TGM2 is overexpressed in MAPKi-resistant melanoma cells and that silencing TGM2 inhibits the proliferation of therapy-resistant melanoma cells. Our results introduce TGM2 as a new vulnerability in therapy-resistant melanoma development and suggest that a combination of MNKi and BETi may address the clinical need for novel therapies targeting unresponsive and drug-resistant melanoma.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_07:00:17.444.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterVincent Richard
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-08-21 08:02:36ID requested
12024-10-01 09:34:05announced
22024-10-22 07:00:17announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: proteomics, TGM2, MNK,LFQ, melanoma, DDA, BET, FAK
Contact List
Christoph H.
contact affiliationSegal Cancer Proteomics Centre, Lady Davis Institute for Medical Research and Jewish General Hospital, and McGill University, Montréal, Québec, Canada Gerald Bronfman Department of Oncology, McGill University, Montréal, Québec, Canada
contact emailchristoph.borchers@mcgill.ca
lab head
Vincent Richard
contact affiliationLady Davis Institute for Medical Research, Jewish General Hospital, McGill University
contact emailvincentroyrichard@gmail.com
dataset submitter
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Dataset FTP location
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