PXD038278-3

PXD038278 is an original dataset announced via ProteomeXchange.

Title	RhoJ controls EMT associated resistance to chemotherapy
Description	The resistance of cancer cells to therapy is responsible for the death of most cancer patients. Epithelial-to-mesenchymal transition (EMT) has been associated with resistance to therapy in different cancer cells. However, the mechanisms by which EMT mediates resistance to therapy remain poorly understood. Here, using a mouse model of skin squamous cell carcinoma (SCC) undergoing spontaneous EMT during tumorigenesis, we found that EMT tumor cells were highly resistant to a wide range of anti-cancer therapy both in-vivo and in-vitro. Using gain and loss of function in vitro and in vivo, we uncovered that RhoJ, a small GTPase preferentially expressed in EMT cancer cells, controls resistance to therapy. Using genome-wide transcriptomic and proteomic profiling, we found that RhoJ regulates EMT associated resistance to chemotherapy by promoting DNA damage response and the formation of new replication forks allowing tumor cells to repair DNA lesions more rapidly and survive under the replicative stress induced by chemotherapy. Using affinity-purification followed by mass spectrometry, we found that RhoJ interacts with proteins regulating nuclear actin and the inhibition of actin polymerization sensitizes EMT tumor cells to chemotherapy induced cell death in a Rhoj dependent manner. Altogether, our study uncovers the role and the mechanisms by which RhoJ acts as a key regulator of EMT associated resistance to chemotherapy.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:45:03.217.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD038278
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sara Dufour
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-22 03:28:29	ID requested
1	2023-01-13 01:12:42	announced
2	2023-04-17 05:52:38	announced	2023-04-17: Updated project metadata.
⏵ 3	2023-11-14 08:45:11	announced	2023-11-14: Updated project metadata.

Debaugnies M, Rodr, í, guez-Acebes S, Blondeau J, Parent MA, Zocco M, Song Y, de Maertelaer V, Moers V, Latil M, Dubois C, Coulonval K, Impens F, Van Haver D, Dufour S, Uemura A, Sotiropoulou PA, M, é, ndez J, Blanpain C, RHOJ controls EMT-associated resistance to chemotherapy. Nature, 616(7955):168-175(2023) [pubmed]

10.6019/PXD038278;

submitter keyword: cancer,Mus musculus (mouse), cell culture, SCC, AP-LC-MS/MS

Cédric Blanpain
contact affiliation	Université libre de Buxelles (ULB), Laboratory of Stem Cells and Cancer, 808 route de Lennik, 1070 Brussels, Belgium ; WELBIO, Université Libre de Bruxelles (ULB), 1070 Bruxelles, Belgium
contact email	Cedric.blanpain@ulb.ac.be
lab head
Sara Dufour
contact affiliation	VIB-UGent
contact email	sara.dufour@vib-ugent.be
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/2023/01/PXD038278

PRIDE project URI

• PRIDE
  1. PXD038278
     1. Label: PRIDE project
     2. Name: RhoJ controls EMT associated resistance to chemotherapy