PXD029467

PXD029467 is an original dataset announced via ProteomeXchange.

Title	Identification of homophilic ATP1A1 interaction between tumor cells and fibroblasts
Description	Tumor cells with diverse phenotype and biological behaviors are influenced by stromal cells through secretory factors or direct cell-cell contact. Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia with fibroblasts as the major cell type. Here, we observed enrichment of myofibroblasts in juxta-tumoral position, where tumor cells gain epithelial-mesenchymal transition for invasion, that correlated with worsened prognosis in PDAC patients. Direct cell-cell contacts as forming heterocellular aggregates between fibroblasts and tumor cells were detected in primary pancreatic tumors and circulating tumor microemboli. Mechanistically, the overexpressed ATP1A1 of tumor cells binds to and reorganizes ATP1A1 of fibroblasts inducing calcium oscillations, NF-κB activation, and activin A secretion. Consequentially, either silencing ATP1A1 expression or neutralizing activin A secretion suppresses tumor invasion and colonization. Taken together, these results elucidate the mechanic interplay between tumor cells and the bound fibroblasts in PDAC progression, and provide opportunities for potential therapeutic strategy against tumor metastasis by blocking such interaction.
HostingRepository	PRIDE
AnnounceDate	2022-06-09
AnnouncementXML	Submission_2022-06-09_04:05:14.920.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD029467
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Yi-Ing Chen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-01 05:00:39	ID requested
⏵ 1	2022-06-09 04:05:15	announced

Chen YI, Chang CC, Hsu MF, Jeng YM, Tien YW, Chang MC, Chang YT, Hu CM, Lee WH, Homophilic ATP1A1 binding induces activin A secretion to promote EMT of tumor cells and myofibroblast activation. Nat Commun, 13(1):2945(2022) [pubmed]

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Human, pancreatic cancer, fibroblast, cell-cell contact, membrane protein, ATP1A1

Wen-Hwa Lee
contact affiliation	Genomics Research Center, Academia Sinica, Taipei, Taiwan. Drug Development Center, China Medical University, Taichung, Taiwan. Department of Biological Chemistry, University of California, Irvine.
contact email	whlee@uci.edu
lab head
Yi-Ing Chen
contact affiliation	Genomics Research Center, Academia Sinica
contact email	eineing@gate.sinica.edu.tw
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/2022/06/PXD029467

PRIDE project URI

• PRIDE
  1. PXD029467
     1. Label: PRIDE project
     2. Name: Identification of homophilic ATP1A1 interaction between tumor cells and fibroblasts