PXD044698-2

PXD044698 is an original dataset announced via ProteomeXchange.

Title	Combined inhibition of MNK signaling and BET proteins reveals TGM2 as a novel vulnerability in melanoma
Description	Melanoma 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_07:00:17.444.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vincent Richard
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-21 08:02:36	ID requested
1	2024-10-01 09:34:05	announced
⏵ 2	2024-10-22 07:00:17	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: proteomics, TGM2, MNK,LFQ, melanoma, DDA, BET, FAK

Christoph H.
contact affiliation	Segal 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 email	christoph.borchers@mcgill.ca
lab head
Vincent Richard
contact affiliation	Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University
contact email	vincentroyrichard@gmail.com
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/2024/10/PXD044698

PRIDE project URI

• PRIDE
  1. PXD044698
     1. Label: PRIDE project
     2. Name: Combined inhibition of MNK signaling and BET proteins reveals TGM2 as a novel vulnerability in melanoma