PXD003223

PXD003223 is an original dataset announced via ProteomeXchange.

Title	Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation
Description	Oncogenic mutations in tumor cells regulate signaling both within tumor cells and heterotypic stromal cells. However, whether oncogenes regulate tumor cell signaling via stromal cells is poorly understood. Here we show that oncogenic KRAS (KRAS-G12D) uniquely regulates tumor cell signaling via stromal cells. By combining cell-specific proteome labeling with phosphoproteomic multiplexing we conducted a multivariate analysis of heterocellular KRAS-G12D signaling in Pancreatic Ductal Adenocarcinoma (PDA) cells. By engaging heterotypic fibroblasts, KRAS-G12D drives unique reciprocal signaling in tumor cells to employ additional kinases and double the number of regulated signaling nodes from cell-autonomous KRAS-G12D. Heterocellular signaling produces a distinct tumor cell phosphoproteome, total proteome, and increase mitochondria capacity via an IGF1R/AXL-AKT axis. Reciprocal KRAS-G12D phenotypes require a heterocellular context and are unreachable by cell-autonomous KRAS-G12D alone. These results demonstrate oncogene signaling should be viewed as a heterocellular process and our existing homocellular perspective underrepresents the extent of oncogene signaling in cancer.
HostingRepository	PRIDE
AnnounceDate	2016-04-19
AnnouncementXML	Submission_2016-04-19_07:01:03.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christopher Tape
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2015-11-20 06:18:00	ID requested
⏵ 1	2016-04-19 07:01:04	announced

Tape CJ, Ling S, Dimitriadi M, McMahon KM, Worboys JD, Leong HS, Norrie IC, Miller CJ, Poulogiannis G, Lauffenburger DA, J, ø, rgensen C, Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation. Cell, 165(4):910-20(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: KRAS PDA phosphoproteomics TMT APE SILAC CTAP

Claus Jorgensen
contact affiliation	Cancer Research UK Manchester Institute
contact email	claus.jorgensen@cruk.manchester.ac.uk
lab head
Christopher Tape
contact affiliation	Institute of Cancer Research
contact email	christopher.tape@icr.ac.uk
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/2016/04/PXD003223

PRIDE project URI

• PRIDE
  1. PXD003223
     1. Label: PRIDE project
     2. Name: Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation