PXD024000

PXD024000 is an original dataset announced via ProteomeXchange.

Title	Inhibition of ß1 integrin induces its association with MT1-MMP and decreases MT1- MMP internalization and cellular invasiveness
Description	Integrin signaling plays a fundamental role in the establishment of focal adhesions and the subsequent formation of invadopodia in malignant cancer cells. Invadopodia facilitate localized adhesion and degradation of the extracellular matrix (ECM), which promote tumour cell invasion and metastasis. Degradation of ECM components is often driven by membrane type-1 matrix metalloproteinase (MT1-MMP), and we have recently shown that regulation of enzyme internalization is dependent on signaling downstream of β1 integrin. Phosphorylation of the cytoplasmic tail of MT1-MMP is required for its internalization and delivery to Rab5-marked early endosomes, where it is then able to be recycled to new sites of invadopodia formation and promote invasion. Here we found that inhibition of β1 integrin, using the antibody AIIB2, inhibited the internalization and recycling of MT1-MMP that is necessary to support long-term cellular invasion. MT1-MMP and β1 integrin were sequestered at the cell surface when β1-integrin was inhibited, and their association under these conditions was detected using immunoprecipitation and mass spectrometry analysis. Sequestration of β1 integrin and MT1-MMP at the cell surface resulted in the formation of large invadopodia and local ECM degradation; however, the impaired internalization and recycling of MT1-MMP and β1 integrin ultimately led to a loss of invasive behaviour.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:15.310.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	2021-02-04 22:35:54	ID requested
1	2022-12-22 09:39:20	announced
⏵ 2	2023-11-14 08:52:15	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Extracellular matrix

integrin

MT1-MMP

invadopodia

Jennifer Geddes-McAlister
contact affiliation	Department of Molecular and Cellular Biology University of Guelph 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/2022/12/PXD024000

PRIDE project URI

• PRIDE
  1. PXD024000
     1. Label: PRIDE project
     2. Name: Inhibition of ß1 integrin induces its association with MT1-MMP and decreases MT1- MMP internalization and cellular invasiveness