PXD005217

PXD005217 is an original dataset announced via ProteomeXchange.

Title	Tenascin-C promotes tumor angiogenesis through pro-angiogenic and anti-angiogenic effects involving YAP, Ephrin-B2 and CXCL12 signaling
Description	In the tumor microenvironment the extracellular matrix molecule tenascin-C is highly expressed which correlates with worsened survival prognosis. Tenascin-C promotes multiple steps in cancer progression. In particular, tenascin-C promotes the tumor angiogenic switch and the formation of more but poorly functional blood vessels by ill defined mechanisms. Here, we studied tenascin-C angio-modulatory functions by tumor and stromal cells. Unexpectedly, we observed that direct contact of endothelial cells with tenascin-C impairs angiogenesis through disruption of actin polymerization. This resulted in cytoplasmic retention of the F-actin sensor and co-transcription factor YAP and led to downregulation of YAP pro-angiogenic target genes. Conversely, tumor cells and carcinoma associated fibroblasts exposed to tenascin-C secreted pro-angiogenic factors that promoted endothelial cell survival and tubulogenesis. We identified and functionally validated CXCL12 and Ephrin- B2 as important pro-angiogenic effectors of tenascin-C. Proteomic analysis of the secretome of tumor cells exposed to tenascin-C revealed a signature that predicts shorter survival of patients with low grade glioma and glioblastoma with a particular significance for a combined expression of tenascin-C and Ephrin-B2. Altogether, we demonstrated a dual mechanism of action of tenascin-C in tumor angiogenesis where direct contact of endothelial cells with tenascin-C impairs angiogenesis, and paracrine signals derived from contact of tumor cells and carcinoma associated fibroblasts with tenascin-C promotes angiogenesis. These opposing effects provide for the first time an explanation of divergent mechanisms controlled by tenascin-C which can result in a denser but less functional tumor blood vasculature and might unveil new targeting and prediction opportunities.
HostingRepository	PRIDE
AnnounceDate	2016-11-07
AnnouncementXML	Submission_2016-11-07_01:12:09.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Oliver Schilling
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-10-24 08:13:42	ID requested
⏵ 1	2016-11-07 01:12:10	announced

Dataset with its publication pending

curator keyword: Biological, Biomedical

submitter keyword: Tenascin

Dr Oliver Schilling
contact affiliation	Institute of Molecular Medicine and Cell Research University of Freiburg Germany
contact email	oliver.schilling@mol-med.uni-freiburg.de
lab head
Oliver Schilling
contact affiliation	University of Freiburg
contact email	oliver.schilling@mol-med.uni-freiburg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005217
     1. Label: PRIDE project
     2. Name: Tenascin-C promotes tumor angiogenesis through pro-angiogenic and anti-angiogenic effects involving YAP, Ephrin-B2 and CXCL12 signaling