PXD068873

PXD068873 is an original dataset announced via ProteomeXchange.

Title	RAB1A is a novel vulnerability in uveal melanoma revealed by dual inhibition of MNK1/2 and mTOR
Description	Uveal melanoma (UM) is a high fatality cancer. It arises in the eye and spreads (metastasizes) to the liver in 50% of affected patients, with a low survival rate of 5 years. In >85% of patients, their ocular tumors have mutations in specific genes, GNAQ and GNA11, leading to tumor progression and metastasis. Conventional therapies such as surgery, chemotherapy, and irradiation halt tumor progression in the eye. Unfortunately, once cancer progresses to metastasis (usually occurring at early stages of the disease), the patients have limited treatment options. Moreover, targeted therapies and immunotherapies fail to achieve more significant survival benefits due to UM's emergence of resistance. Therefore, there is an urgent need to develop new therapeutic strategies to treat UM. This project explores the use of 2 small molecule inhibitors , which suppresses MNK1/2-eIF4E (SEL201) and mTORC1/2-4EBP1 (INK128), as a strategy to block the progression of UM to invasive and metastatic disease. Our data shows that both inhibitors work in concert to decrease clonogenicity and invasiveness of some, but not all, UM cell lines screened. To define the mechanism by which MNK1/2 blockade augments the efficacy of mTOR inhibitors in UM, we performed a discovery approach where T128 UM cells were treated with the drug combination for 24h and sent for DIA MS analysis. The analysis showed that protein vesicle trafficking, driven mainly RAB1A, was being downregulated in the combination treatment, which translated to decreased invasive and clonogenic potential.
HostingRepository	PRIDE
AnnounceDate	2026-02-20
AnnouncementXML	Submission_2026-02-20_10:32:30.103.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Raul Ernesto Flores Gonzalez
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-26 12:13:25	ID requested
⏵ 1	2026-02-20 10:32:31	announced

Flores-Gonz, á, lez RE, Goncalves C, Wirasinghe N, Gaudreault V, Noda Ferro JM, Coutant K, Mitchell A, Papadopoulos T, Cho YY, Guettler E, Gonz, á, lez-Moreno DR, Preston S, Cai F, Gagnon N, Jean S, Landreville S, Miller WH, Del Rinc, ó, n SV, RAB1A is a novel vulnerability in uveal melanoma revealed by dual inhibition of MNK1/2 and mTOR. Cell Death Differ, ():(2026) [pubmed]

10.1038/s41418-026-01684-y;

submitter keyword: uveal melanoma, liver metastasis.,MNK1/2, RAB1A, mTOR

Sonia del Rincon
contact affiliation	Lady Davis Institute for Medical Research - Jewish General Hospital - McGill University
contact email	soniavictoria.delrincon@mcgill.ca
lab head
Raul Ernesto Flores Gonzalez
contact affiliation	Lady Davis Institute-Jewish General Hospital - McGill University
contact email	raul.floresgonzalez2@mail.mcgill.ca
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/2026/02/PXD068873

PRIDE project URI

• PRIDE
  1. PXD068873
     1. Label: PRIDE project
     2. Name: RAB1A is a novel vulnerability in uveal melanoma revealed by dual inhibition of MNK1/2 and mTOR