PXD051666

PXD051666 is an original dataset announced via ProteomeXchange.

Title	Secretome from TXNIP knockout human colorectal cell line (DLD1)
Description	Chemotherapy, the standard of care treatment for cancer patients with advanced disease, has been increasingly recognised to activate host immune responses to produce durable outcomes. Here, in colorectal adenocarcinoma (CRC) we identify oxaliplatin-induced Thioredoxin Interacting Protein (TXNIP), a MondoA-dependent tumor suppressor gene, as a negative regulator of Growth/Differentiation Factor 15 (GDF15). GDF15 is a negative prognostic factor in CRC and promotes the differentiation of regulatory T cells (Tregs), which inhibit CD8 T cell activation. Intriguingly, multiple models including patient-derived tumor organoids demonstrate that the loss of TXNIP and GDF15 responsiveness to oxaliplatin is associated with advanced disease or chemotherapeutic resistance, with transcriptomic or proteomic GDF15/TXNIP ratios showing potential as a prognostic biomarker. These findings illustrate a potentially common pathway where chemotherapy-induced epithelial oxidative stress drives local immune remodelling for patient benefit, with disruption of this pathway seen in refractory or advanced cases.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:54:42.271.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Richard Beatson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-23 07:31:28	ID requested
1	2024-08-12 03:03:28	announced
⏵ 2	2024-10-22 06:54:43	announced	2024-10-22: Updated project metadata.

10.1038/s44321-024-00105-2;

Deng J, Pan T, Wang D, Hong Y, Liu Z, Zhou X, An Z, Li L, Alfano G, Li G, Dolcetti L, Evans R, Vicencio JM, Vlckova P, Chen Y, Monypenny J, Gomes CAC, Weitsman G, Ng K, McCarthy C, Yang X, Hu Z, Porter JC, Tape CJ, Yin M, Wei F, Rodriguez-Justo M, Zhang J, Tejpar S, Beatson R, Ng T, The MondoA-dependent TXNIP/GDF15 axis predicts oxaliplatin response in colorectal adenocarcinomas. EMBO Mol Med, 16(9):2080-2108(2024) [pubmed]

submitter keyword: Human, TXNIP, colorectal, secreted

Tony Ng
contact affiliation	Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, UK. UCL Cancer Institute, University College London, London, United Kingdom. Cancer Research UK City of London Centre. GSK
contact email	tony.ng@kcl.ac.uk
lab head
Richard Beatson
contact affiliation	King's College London
contact email	richard.1.beatson@kcl.ac.uk
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/2024/08/PXD051666

PRIDE project URI

• PRIDE
  1. PXD051666
     1. Label: PRIDE project
     2. Name: Secretome from TXNIP knockout human colorectal cell line (DLD1)