PXD018253 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-03-30 00:27:21 | ID requested | |
⏵ 1 | 2020-05-27 00:55:34 | announced | |
Publication List
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] |
Keyword List
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) |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD018253
- Label: PRIDE project
- Name: Selective activation of PERK signaling mediates fibroblast education and tumor progression by a CRELD2-dependent mechanism