PXD070860

PXD070860 is an original dataset announced via ProteomeXchange.

Title	DHODH inhibition suppresses cutaneous squamous cell carcinoma growth by the induction of differentiation through perturbation of the cellular redox balance
Description	Dihydroorotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine biosynthesis, has recently emerged as a therapeutic target in various cancers. We have previously identified a pivotal role of DHODH in initiation of cutaneous squamous cell carcinoma (cSCC), the second most common type of non-melanoma skin cancer. However, the key mechanisms driving the anticancer activity of DHODH inhibition remain unexplored in cSCC. To evaluate the impact of DHODH inhibition on cSCC growth, we employed three complementary approaches: (1) pharmacological inhibition of DHODH in mice bearing xenografts of A431 and SCC13 cells through oral administration of leflunomid (LFN) or PTC299 (PTC), and (2) genetic silencing of DHODH via transduction of cells with a lentiviral vector expressing shRNA targeting DHODH (shDHODH) prior to transplantation into NSG mice. After transplantation of A431 or SCC13 cells and once tumors reached an average volume of 150 to 200 mm3, mice were divided into two groups that receiving either vehicle alone or LFN administrated orally on a daily basis. The same procedure was applied for treatment with PTC299. To further investigate, DHODH expression was downregulated in A431 and SCC13 cells using shDHODH. Cells transduced with shCtrol used as control. Six days after transduction, the cells were subcutaneously engrafted into NSG mice. To investigate the molecular consequences of DHODH inhibition across distinct cSCC models, label-free quantitative proteomic analyses were performed on A431 and SCC13 xenografts treated with LFN or PTC299, as well as on tumors transduced with shDHODH (6 xenografts per group).
HostingRepository	PRIDE
AnnounceDate	2026-06-15
AnnouncementXML	Submission_2026-06-14_22:41:16.632.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephane Claverol
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-17 16:17:59	ID requested
⏵ 1	2026-06-14 22:41:17	announced

10.1038/s41419-026-08815-w;

Khalife F, Muzotte E, Naji F, Mahfouf W, Izotte J, Pinson B, Claverol S, Amoedo N, Fayyad-Kazan H, Dousset L, Rossignol R, Rezvani HR, DHODH inhibition suppresses cutaneous squamous cell carcinoma growth by the induction of differentiation through perturbation of the cellular redox balance. Cell Death Dis, 17(1):(2026) [pubmed]

submitter keyword: cSCC, cutaneous squamous cell carcinoma, differentiation, pyrimidine biosynthesis, cancer therapy,DHODH

Stephane Claverol
contact affiliation	Univ. Bordeaux, Bordeaux Proteome, Bordeaux, France
contact email	stephane.claverol@u-bordeaux.fr
lab head
Stephane Claverol
contact affiliation	Bordeaux Proteome
contact email	stephane.claverol@u-bordeaux.fr
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/2026/06/PXD070860

PRIDE project URI

• PRIDE
  1. PXD070860
     1. Label: PRIDE project
     2. Name: DHODH inhibition suppresses cutaneous squamous cell carcinoma growth by the induction of differentiation through perturbation of the cellular redox balance