PXD012952

PXD012952 is an original dataset announced via ProteomeXchange.

Title	Neocarzilin A is a potent inhibitor of cancer cell motility targeting VAT-1 controlled pathways
Description	The natural product neocarzilin A (NCA) was discovered decades ago and despite its potent cytotoxic effects no mode of action studies were performed up to date. Synthesis of neocarzilins A, B, C and a stereoisomer of NCA provided insights into structural preferences as well as access to probes for functional studies. NCA pertained as the most active member and was not only effective against cell proliferation but also migration, a novel and so far overlooked activity. The potent anti-migratory effects could also be confirmed in an in vivo breast carcinoma mouse model. To decipher the molecular mode of action, we applied chemical proteomics for target discovery and revealed that NCA interrogates cancer cell migration via irreversible binding to the largely uncharacterized synaptic vesicle membrane protein VAT-1. A corresponding knockout of the protein confirmed the phenotype and pull-down studies showed the interaction with an intricate network of key migration mediators such as Talin-1. Overall, we introduce VAT-1 as a promising novel target for the development of selective migration inhibitors with the perspective to limit toxicity in absence of anti-proliferative effects.
HostingRepository	PRIDE
AnnounceDate	2019-08-23
AnnouncementXML	Submission_2019-08-23_07:39:22.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Carolin Gleissner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-05 00:48:42	ID requested
⏵ 1	2019-08-23 07:39:24	announced

Gleissner CM, Pyka CL, Heydenreuter W, Gronauer TF, Atzberger C, Korotkov VS, Cheng W, Hacker SM, Vollmar AM, Braig S, Sieber SA, Neocarzilin A Is a Potent Inhibitor of Cancer Cell Motility Targeting VAT-1 Controlled Pathways. ACS Cent Sci, 5(7):1170-1178(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: Target identification, chemical proteomics, natural compound, tumor cell migration

Stephan A. Sieber
contact affiliation	Center for Integrated Protein Science at the Department of Chemistry, Technische Universität München, Garching b. München 85747, Germany; Chair of Organic Chemistry II, Technische Universität München, Garching b. München 85747, Germany
contact email	stephan.sieber@tum.de
lab head
Carolin Gleissner
contact affiliation	TU München
contact email	Carolin.Gleissner@tum.de
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/2019/08/PXD012952

PRIDE project URI

• PRIDE
  1. PXD012952
     1. Label: PRIDE project
     2. Name: Neocarzilin A is a potent inhibitor of cancer cell motility targeting VAT-1 controlled pathways