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PXD033356-2

PXD033356 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNCOA4-mediated ferritinophagy is a pancreatic cancer dependency via maintenance of iron bioavailability for iron-sulfur cluster proteins
DescriptionOncogenic KRAS rewires pancreatic ductal adenocarcinoma (PDAC) metabolism to promote dependence on autophagy and iron metabolism. NCOA4-mediated ferritinophagy links autophagy and iron metabolism as NCOA4 selectively targets ferritin, the cellular iron storage complex, via autophagy to the lysosome for ferritin degradation and release of iron for utilization. Using patient-derived and genetically engineered murine models of PDAC we now demonstrate that ferritinophagy is upregulated in PDAC to sustain iron availability thereby promoting PDAC progression. PDAC global quantitative proteomics reveals that ferritinophagy fuels iron-sulfur cluster synthesis to support mitochondrial homeostasis. Targeting NCOA4 leads to tumor growth delay and prolonged survival but with development of compensatory iron acquisition pathways. Finally, a ferritinophagy gain-of-function PDAC murine model demonstrates worse survival, and an elevated ferritinophagy expression signature predicts for worse overall survival in human PDAC patients. Together, our data define NCOA4-mediated ferritinophagy as a therapeutic target in PDAC and reveal that maintenance of cellular iron homeostasis is a critical cell autonomous function of PDAC autophagy.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:56:46.131.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMiljan Kuljanin
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-04-21 07:12:03ID requested
12022-08-17 07:13:04announced
22023-11-14 08:56:46announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: ferritinophagy,NCOA4, iron, PDAC
Contact List
Joseph D. Mancias1
contact affiliationDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA 02115
contact emailJoseph_Mancias@dfci.harvard.edu
lab head
Miljan Kuljanin
contact affiliationHarvard Medical School
contact emailmiljan_kuljanin@hms.harvard.edu
dataset submitter
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Dataset FTP location
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