PXD033356-1

PXD033356 is an original dataset announced via ProteomeXchange.

Title	NCOA4-mediated ferritinophagy is a pancreatic cancer dependency via maintenance of iron bioavailability for iron-sulfur cluster proteins
Description	Oncogenic 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.
HostingRepository	PRIDE
AnnounceDate	2022-08-17
AnnouncementXML	Submission_2022-08-17_07:13:04.298.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Miljan Kuljanin
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-21 07:12:03	ID requested
⏵ 1	2022-08-17 07:13:04	announced
2	2023-11-14 08:56:46	announced	2023-11-14: Updated project metadata.

10.1158/2159-8290.CD-22-0043;

submitter keyword: NCOA4, ferritinophagy, iron, PDAC

Joseph D. Mancias1
contact affiliation	Division 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 email	Joseph_Mancias@dfci.harvard.edu
lab head
Miljan Kuljanin
contact affiliation	Harvard Medical School
contact email	miljan_kuljanin@hms.harvard.edu
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/2022/08/PXD033356

PRIDE project URI

• PRIDE
  1. PXD033356
     1. Label: PRIDE project
     2. Name: NCOA4-mediated ferritinophagy is a pancreatic cancer dependency via maintenance of iron bioavailability for iron-sulfur cluster proteins