PXD058352-1

PXD058352 is an original dataset announced via ProteomeXchange.

Title	Investigation of signalling pathways and potential mechanisms of drug resistance associated with the two transmissible cancers in the Tasmanian devil using phosphoproteomics
Description	Investigation of signalling pathways and potential mechanisms of drug resistance associated with the two transmissible cancers in the Tasmanian devil using phosphoproteomics Two transmissible cancers, Devil Facial Tumor 1 (DFT1) and Devil Facial Tumor 2 (DFT2), have caused significant declines in Tasmanian devil populations. DFT1 is driven by ERBB tyrosine kinases, immune evasion through MHCI downregulation and can be targeted by ERBB inhibition. In contrast, DFT2 is susceptible to PDGFR inhibition. We show that both tumors exhibit changes in upstream kinase phosphorylation but activate common downstream pathways, enabling rapid development of escape mechanisms. DFT1 shifts toward a more mesenchymal phenotype and PDGFR signaling when ERBB is inhibited, resembling DFT2, while DFT2 adapts to mimic ERBB/STAT3 signaling and MHCI-related immune evasion when PDGFR is inhibited, resembling DFT1. This tumor plasticity, particularly in DFT2, mirrors changes observed in the wild, offering insights into the future evolution of these cancers. Importantly, combination treatments targeting both pathways show synergistic effects, providing a potential strategy for conservation efforts for the endangered Tasmanian devil.
HostingRepository	PRIDE
AnnounceDate	2026-03-09
AnnouncementXML	Submission_2026-03-08_20:18:11.738.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Richard Wilson
SpeciesList	scientific name: Sarcophilus harrisii; NCBI TaxID: NEWT:9305;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-27 16:29:39	ID requested
⏵ 1	2026-03-08 20:18:12	announced

10.1038/s44318-025-00603-0;

Sch, ö, nbichler A, Orlova A, Kreindl C, Endler L, Wilson R, Kosack L, Hofmann A, Viczenczova C, Darby J, Erdogan F, Patchett AL, Koren A, Kubicek S, M, ü, ller M, Flies AS, Bergthaler A, Moriggl R, Tyrosine kinase targeting uncovers oncogenic pathway plasticity in Tasmanian devil transmissible cancers. EMBO J, 45(5):1426-1459(2026) [pubmed]

submitter keyword: kinase inhibitor resistance, receptor tyrosine kinase inhibition, Tasmanian devils, transmissible cancer, xenograft,Devil facial tumour disease, phosphoproteomics, PDGFR, ERBB

Dr Richard Wilson
contact affiliation	Proteomics facility, Central Science Laboratory, University of Tasmania
contact email	richard.wilson@utas.edu.au
lab head
Richard Wilson
contact affiliation	University of Tasmania
contact email	richard.wilson@utas.edu.au
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/2026/03/PXD058352

PRIDE project URI

• PRIDE
  1. PXD058352
     1. Label: PRIDE project
     2. Name: Investigation of signalling pathways and potential mechanisms of drug resistance associated with the two transmissible cancers in the Tasmanian devil using phosphoproteomics