PXD030879-1

PXD030879 is an original dataset announced via ProteomeXchange.

Title	Gasdermin E mediates resistance of pancreatic adenocarcinoma to enzymatic digestion through a YBX1-mucin pathway
Description	Pancreatic ductal adenocarcinoma (PDAC) originates from normal pancreatic ducts where digestive juice is regularly produced. It remains unclear how PDAC can escape auto-digestion by digestive enzymes. Here we show that human PDAC tumor cells use gasdermin E (GSDME), a pore-forming protein upon caspase 3 cleavage, to mediate the digestive resistance. We find that GSDME facilitates the expression of mucins 1 and 13 in pancreatic tumor cells, which forms a barrier to prevent chymotrypsin-mediated destruction. Inoculation of GSDME-/- PDAC cells results in subcutaneous but not orthotopic tumor formation in mice. Either inhibiting or knocking out MUC1 or MUC13 abrogates orthotopic PDAC growth in NOD-SCID mice. Mechanistically, GSDME interacts with and transports transcription factor YBX1 into the nucleus where YBX1 directly promotes mucin expression. This GSDME-YBX1-mucin axis is also confirmed in PDAC patients. These findings uncover a unique survival mechanism of PDAC cells in pancreatic microenvironments, thus providing a potential target for PDAC treatment.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-20_04:56:18.130.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yabo Zhou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-11 01:08:59	ID requested
⏵ 1	2022-05-20 04:56:18	announced

Lv J, Liu Y, Mo S, Zhou Y, Chen F, Cheng F, Li C, Saimi D, Liu M, Zhang H, Tang K, Ma J, Wang Z, Zhu Q, Tong WM, Huang B, Gasdermin E mediates resistance of pancreatic adenocarcinoma to enzymatic digestion through a YBX1-mucin pathway. Nat Cell Biol, 24(3):364-372(2022) [pubmed]

submitter keyword: GSDME，Pancreatic Ductal Adenocarcinoma，YBX1,MUCIN

Bo Huang
contact affiliation	Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing
contact email	tjhuangbo@hotmail.com
lab head
Yabo Zhou
contact affiliation	Chinese Academy of Medical Sciences
contact email	yabozzz@foxmail.com
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/2022/05/PXD030879

PRIDE project URI

• PRIDE
  1. PXD030879
     1. Label: PRIDE project
     2. Name: Gasdermin E mediates resistance of pancreatic adenocarcinoma to enzymatic digestion through a YBX1-mucin pathway