PXD039276

PXD039276 is an original dataset announced via ProteomeXchange.

Title	Cancer Cell Extravasation Requires iPlectin Mediated Choreography of MT1-MMP at Invadopodia
Description	Cancer cell extravasation is a key step of the metastatic cascade and an attractive therapeutic opportunity. Early steps in cancer cell extravasation require formation of tentacle-like protrusions called invadopodia that physically breach the endothelial barrier and degrade extracellular matrix (ECM). However, the mechanisms by which invadopodia-specific proteases such as MT1-MMP are called to invadopodia are unclear. In integrin-activated metastatic breast cancer cells, MT1-MMP was found to associate with plectin, a cytoskeletal linker protein, and vimentin, an intermediate filament (IF) protein. Interestingly, complex formation between plectin MT1-MMP immediately launches invadopodia formation, a subtype we termed iplectin (i=invadopodial). iPlectin (complexes of plectin and MT1-MMP) and vimentin cooperate to deliver and anchor this form of MT1-MMP to invadopodia. Genetic depletion of plectin significantly reduced invadopodia formation and significantly reduced cell invasion in vitro. To ascertain the effects of depleted plectin on metastatic behavior, in vivo extravasation efficiency assays and intravital imaging methods were performed. These assays revealed iplectin to be a key component of invadopodia ultrastructure; loss of plectin abrogated cancer cell extravasation rates. Pharmacological inhibition of plectin using the novel small molecule Plecstatin-1 (PST-1) altered vimentin and microtubule networks and altered MT1-MMP delivery to F-actin puncta, presumably due to inhibition of iplectin. In terms of metastasis dynamics, PST-1 treatment reduced invadopodia formation and extravasation rates. Hence, iplectin is responsible for MT1-MMP being called to invadopodia and the most therapeutically relevant form of plectin.
HostingRepository	PRIDE
AnnounceDate	2025-03-28
AnnouncementXML	Submission_2025-03-28_07:52:12.914.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Geddes-McAlister
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-05 05:43:41	ID requested
⏵ 1	2025-03-28 07:52:13	announced

10.1038/s41416-024-02782-9;

Grafinger OR, Hayward JJ, Meng Y, Geddes-McAlister J, Li Y, Mar S, Sheng M, Su B, Thillainadesan G, Lipsman N, Coppolino MG, Trant JF, Jerzak KJ, Leong HS, plectin-mediated delivery of MT1-MMP at invadopodia. Br J Cancer, 131(5):931-943(2024) [pubmed]

submitter keyword: invadopodia,cancer, protein-protein interactions

Jennifer Geddes-McAlister
contact affiliation	Molecular and Cellular Biology Department, University of Guelph, 50 Stone Rd. E. Guelph, Ontario, Canada, N1G 2W1
contact email	jgeddesm@uoguelph.ca
lab head
Jennifer Geddes-McAlister
contact affiliation	University of Guelph
contact email	jgeddesm@uoguelph.ca
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/2025/03/PXD039276

PRIDE project URI

• PRIDE
  1. PXD039276
     1. Label: PRIDE project
     2. Name: Cancer Cell Extravasation Requires iPlectin Mediated Choreography of MT1-MMP at Invadopodia