PXD032257

PXD032257 is an original dataset announced via ProteomeXchange.

Title	Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer
Description	Aberrant activation of the ERK signaling pathway triggers a protective anticancer response characterized by stable growth arrest and activation of tumor suppressors called cellular senescence. Pancreatic adenocarcinomas (PDAC) often possess mutations in K-Ras that activate the ERK pathway. Pancreatic intraepithelial neoplasia of low degree display high levels of phospho-ERK consistent with senescence acting as a barrier for malignant transformation. However, advanced lesions downregulate phospho-ERK levels circumventing the senescence barrier. Restoring ERK hyperactivation in PDAC using an activated allele of the kinase RAF, leads to ERK-dependent growth arrest with senescence biomarkers. Phosphoproteomics analysis of ERK-dependent senescence in PDAC revealed a decrease in several nucleolar phosphoproteins suggesting that high levels of ERK lead to senescence via nucleolar stress. Consistent with this explanation, ERK-dependent senescent cells displayed intranucleolar foci containing RNA polymerase I. Combining ribosome biogenesis inhibitors with ERK hyperactivation reinforced the senescence response of PDAC cells. The drug cocktail FOLFIRINOX, currently the best treatment for PDAC, also triggered ERK hyperactivation and nucleolar stress characterized by nucleolar foci, solid amyloid aggregates and a decrease in 5.8S and 28S rRNAs. We thus suggest that drugs targeting ribosome biogenesis can improve the senescence anticancer response in pancreatic cancer.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:44:20.578.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD032257
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Eric Bonneil
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-14 08:53:04	ID requested
1	2024-06-10 13:11:17	announced
⏵ 2	2024-10-22 06:44:21	announced	2024-10-22: Updated project metadata.

Rowell MC, Desch, ê, nes-Simard X, Lopes-Paciencia S, Le Calv, é B, Kalegari P, Mignacca L, Fernandez-Ruiz A, Guillon J, Lessard F, Bourdeau V, Igelmann S, Duman AM, Stanom Y, Kottakis F, Deshpande V, Krizhanovsky V, Bardeesy N, Ferbeyre G, Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer. Cell Cycle, 22(19):2172-2193(2023) [pubmed]

10.6019/PXD032257;

10.1080/15384101.2023.2278945;

submitter keyword: ERK

pancreatic cancer

senescence

nucleolar stress

ribosome biogenesis

RNA polymerase I

Gerado Ferbeyre
contact affiliation	Département de biochimie Faculté de Médecine Université de Montréal
contact email	g.ferbeyre@umontreal.ca
lab head
Eric Bonneil
contact affiliation	Proteomic Platform
contact email	eric.bonneil@umontreal.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/2024/06/PXD032257

PRIDE project URI

• PRIDE
  1. PXD032257
     1. Label: PRIDE project
     2. Name: Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer