PXD020269

PXD020269 is an original dataset announced via ProteomeXchange.

Title	Proteolytic processing converts pro-tumorigenic Angiopoietin-like 4 into an inhibitor of metastasis
Description	Preclinical and clinical studies have solidly established the concepts of concomitant tumor resistance (CTR), the inhibition of metastases formation by the primary tumor. Yet, the mechanisms of CTR are poorly understood and bench-to-bedside studies are largely missing. Here, we show that proteolytic processing of ANGPTL4 liberated the potent CTR-inducing capacity of the N-terminal cleavage fragment, nANGPTL4. Full-length ANGPTL4 was primarily detected in tumor tissues, whereas nANGPTL4 predominated in the systemic circulation, whose concentrations correlated inversely with disease progression. Comparative studies in multiple preclinical tumor models revealed distinctly opposing functions of the ANGPTL4 cleavage fragments. Full length and cANGPTL4 promoted tumor growth and metastasis leading to reduced overall survival. Conversely, nANGPTL4 inhibited metastasis formation and enhanced overall survival. The experiments identified proteolytic cleavage as regulatory mechanism converting pro-tumorigenic ANGPTL4 into anti-metastatic nANGPTL4. Moreover, the results revitalize the concept that primary tumors may suppress metastases through systemic release of metastasis-inhibiting cytokines
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:51:22.440.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD020269
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alexander Schmidt
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-09 02:21:08	ID requested
1	2022-10-16 23:37:09	announced
⏵ 2	2023-11-14 08:51:22	announced	2023-11-14: Updated project metadata.

10.6019/PXD020269;

submitter keyword: PRM, LC-MS,Angptl4

Alexander Schmidt
contact affiliation	Biozentrum, University of Basel, Switzerland
contact email	alex.schmidt@unibas.ch
lab head
Alexander Schmidt
contact affiliation	Proteomics Core Facility
contact email	alex.schmidt@unibas.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020269
     1. Label: PRIDE project
     2. Name: Proteolytic processing converts pro-tumorigenic Angiopoietin-like 4 into an inhibitor of metastasis