PXD018253

PXD018253 is an original dataset announced via ProteomeXchange.

Title	Selective activation of PERK signaling mediates fibroblast education and tumor progression by a CRELD2-dependent mechanism
Description	It is now well-accepted that cancers co-opt the microenvironment to support their growth. However, the molecular mechanisms underlying cancer-microenvironment interactions remain poorly defined. We have found that Rho-associated kinase (ROCK) activity in the epithelial component of mammary tumors selectively actuates Protein kinase R-like endoplasmic reticulum kinase (Perk), causing the recruitment and persistent education of tumor-promoting cancer-associated fibroblasts (CAFs), a key component of the cancer microenvironment. Analysis of tumors from mice and human patients identified Cysteine-rich with EGF-like domains 2 (CRELD2), as the paracrine factor underlying PERK-mediated CAF-education downstream of ROCK. CRELD2 expression was found to be regulated by ATF4 downstream of the PERK pathway and knock-down of CRELD2 prevented tumor progression, demonstrating that the paracrine ROCK-PERK-ATF4-CRELD2 axis is a promoter of breast cancer progression and suggesting new therapeutic opportunities.
HostingRepository	PRIDE
AnnounceDate	2020-05-27
AnnouncementXML	Submission_2020-05-27_00:55:33.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jarrod Sandow
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-30 00:27:21	ID requested
⏵ 1	2020-05-27 00:55:34	announced

Boyle ST, Poltavets V, Kular J, Pyne NT, Sandow JJ, Lewis AC, Murphy KJ, Kolesnikoff N, Moretti PAB, Tea MN, Tergaonkar V, Timpson P, Pitson SM, Webb AI, Whitfield RJ, Lopez AF, Kochetkova M, Samuel MS, ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism. Nat Cell Biol, 22(7):882-895(2020) [pubmed]

submitter keyword: Breast cancer, endoplasmic reticulum (ER)stress, unfolded protein response 25 (UPR), integrated stress response (ISR), cancer progression, ROCK, PERK, 26 extracellular matrix, tumor microenvironment, cancer-associated fibroblasts (CAFs)

Michael Samuel
contact affiliation	Centre for Cancer Biology, SA Pathology and the University of South Australia, Adelaide SA 5000, Australia
contact email	Michael.Samuel@unisa.edu.au
lab head
Jarrod Sandow
contact affiliation	WEHI
contact email	sandow@wehi.edu.au
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/2020/05/PXD018253

PRIDE project URI

• PRIDE
  1. PXD018253
     1. Label: PRIDE project
     2. Name: Selective activation of PERK signaling mediates fibroblast education and tumor progression by a CRELD2-dependent mechanism