PXD050453

PXD050453 is an original dataset announced via ProteomeXchange.

Title	Neocarzilin inhibits cancer cell proliferation via BST-2 degradation resulting in lipid raft trapped EGFR
Description	Neocarzilin (NCA) is a natural product exhibiting potent anti-migratory as well as anti-proliferative effects. While the vesicle amide transport protein 1 (VAT-1) was previously shown to inhibit migration upon NCA binding, the molecular mechanisms responsible for impaired proliferation remained elusive. We here introduce a chemical probe closely resembling the structural and stereochemical features of NCA and unravel bone marrow stromal antigen 2 (BST-2) as a second major target in cancer cells. The antiproliferative mechanism of NCA was confirmed in corresponding BST-2 knockout (KO) cells which were less sensitive to compound treatment. Vice versa, overexpression of the target in the KO reduced proliferation comparable to wild type (wt) cells. Whole proteome mass-spectrometric (MS) analysis of NCA treated wt and KO cancer cells unraveled affected pathways linked to EGFR signaling and demonstrated reduced levels of BST-2 upon NCA treatment. In-depth analysis of BST-2 levels in response to proteasome and lysosome inhibitors, confirmed a lysosomal degradation path upon NCA treatment. As BST-2 is mediating the release of EGFR from lipid rafts to turn on proliferation signaling pathways, reduced BST-2 levels led to attenuated phosphorylation of EGFR and downstream targets. Furthermore, fluorescence microscopy confirmed colocalization of BST-2 and lipid rafts in presence of NCA. Overall, NCA represents a versatile anti-cancer natural product with a unique dual mode of action and unconventional inhibition of proliferation via BST-2 degradation.
HostingRepository	PRIDE
AnnounceDate	2024-11-26
AnnouncementXML	Submission_2024-11-26_07:53:25.149.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Josef Braun
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Eclipse; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-07 09:47:11	ID requested
⏵ 1	2024-11-26 07:53:25	announced

10.1021/JACSAU.4C00039;

submitter keyword: natural products, cancer, proteomics, antitumor agents, biological activity

Prof. Dr. Stephan Sieber
contact affiliation	TUM School of Natural Sciences, Department of Bioscience, Center for Functional Protein Assemblies (CPA), Technical University of Munich (TUM), Ernst-Otto-Fischer Straße 8, Garching near Munich, D-85748, Germany
contact email	stephan.sieber@tum.de
lab head
Josef Braun
contact affiliation	Center for Protein Assemblies (CPA), Department of Chemistry, Chair of Organic Chemistry II, Technical University of Munich, Ernst-Otto-Fischer-Str. 8, Garching, D 85748, Germany
contact email	braun.josef@mytum.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050453
     1. Label: PRIDE project
     2. Name: Neocarzilin inhibits cancer cell proliferation via BST-2 degradation resulting in lipid raft trapped EGFR