PXD022311

PXD022311 is an original dataset announced via ProteomeXchange.

Title	Cancer-secreted miRNAs regulate amino-acid-induced mTORC1 signaling and fibroblast protein synthesis
Description	Metabolic reprogramming of non-cancer cells residing in a tumor microenvironment, as a result of the adaptations to cancer-derived metabolic and non-metabolic factors, is an emerging aspect of cancer-host interaction. We show that in normal and cancer-associated fibroblasts, breast-cancer-secreted extracellular vesicles suppress mTOR signaling upon amino acid stimulation to globally reduce mRNA translation. This is through delivery of cancer-derived miR-105 and miR-204, which target RAGC, a component of Rag GTPases that regulate mTORC1 signaling. Following amino acid starvation and subsequent re-feeding, 13C-arginine labeling of de novo synthesized proteins shows selective translation of proteins that cluster to specific cellular functional pathways. The repertoire of these newly synthesized proteins is altered in fibroblasts treated with cancer-derived extracellular vesicles, in addition to the overall suppressed protein synthesis. In human breast tumors, RAGC protein levels are inversely correlated with miR-105 in the stroma. Our results suggest that through educating fibroblasts to reduce and re-prioritize mRNA translation, cancer cells rewire the metabolic fluxes of amino acid pool and dynamically regulate stroma-produced proteins during periodic nutrient fluctuations.
HostingRepository	PRIDE
AnnounceDate	2020-11-24
AnnouncementXML	Submission_2021-01-04_01:09:48.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Majid Ghassemian
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	6x(13)C labeled residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-03 05:28:55	ID requested
1	2020-11-23 23:11:22	announced
⏵ 2	2021-01-04 01:09:49	announced	2021-01-04: Updated publication reference for PubMed record(s): 33345445.

Fong MY, Yan W, Ghassemian M, Wu X, Zhou X, Cao M, Jiang L, Wang J, Liu X, Zhang J, Wang SE, Cancer-secreted miRNAs regulate amino-acid-induced mTORC1 signaling and fibroblast protein synthesis. EMBO Rep, 22(2):e51239(2021) [pubmed]

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

submitter keyword: mouse, silac, mass spec

Emily Wang
contact affiliation	Moores Cancer Center; University of California San Diego; La Jolla, CA 92093; USA, Department of Pathology; University of California San Diego; La Jolla, CA 92093
contact email	emilywang@health.ucsd.edu
lab head
Majid Ghassemian
contact affiliation	Moores Cancer Center; University of California San Diego
contact email	mghassem@ucsd.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/2020/11/PXD022311

PRIDE project URI

• PRIDE
  1. PXD022311
     1. Label: PRIDE project
     2. Name: Cancer-secreted miRNAs regulate amino-acid-induced mTORC1 signaling and fibroblast protein synthesis