PXD023867

PXD023867 is an original dataset announced via ProteomeXchange.

Title	Serine-threonine kinase TAO3 mediated trafficking of endosomes containing the invadopodia scaffold TKS5-alpha promotes cancer invasion and tumor growth
Description	Invadopodia are actin-based proteolytic membrane protrusions required for invasive behavior and tumor growth. In this study, we used our high-content screening assay to identify kinases whose activity impacts invadopodia formation. Among the top hits selected for further analysis was TAO3, a STE20-like kinase of the GCK subfamily, for further analysis. TAO3 was overexpressed in many human cancers, and regulated invadopodia formation in melanoma, breast and bladder cancers. Furthermore, TAO3 catalytic activity facilitated melanoma growth in 3-dimensional matrices and in vivo. A novel, potent catalytic inhibitor of TAO3 was developed that inhibited invadopodia formation and function, and tumor cell extravasation, and growth. Treatment with these inhibitors demonstrated that TAO3 activity is required for endosomal trafficking of TKS5-alpha, an obligate invadopodia scaffold protein. A phosphoproteomics screen for TAO3 substrates revealed the dynein subunit protein LIC2 as a relevant substrate. Knockdown of LIC2 or expression of a phosphomimetic form promoted invadopodia formation. Thus, TAO3 is a new therapeutic target with a distinct mechanism of action.
HostingRepository	PRIDE
AnnounceDate	2021-01-29
AnnouncementXML	Submission_2021-01-29_04:38:33.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-28 04:06:57	ID requested
1	2021-01-28 09:17:23	announced
2	2021-01-29 04:37:15	announced	2021-01-29: Updated project metadata.
⏵ 3	2021-01-29 04:38:34	announced	2021-01-29: Updated project metadata. 2021-01-29: Updated publication reference for PubMed record(s): 33414172.

Iizuka S, Quintavalle M, Navarro JC, Gribbin KP, Ardecky RJ, Abelman MM, Ma CT, Sergienko E, Zeng FY, Pass I, Thomas GV, McWeeney SK, Hassig CA, Pinkerton AB, Courtneidge SA, Promotes Cancer Invasion and Tumor Growth. Cancer Res, 81(6):1472-1485(2021) [pubmed]

submitter keyword: TAO3, TAOK3, invadopodia, TKS5-alpha, endosomes, TMT data, Orbitrap Fusion, phosphoproteomics, PTM Quantitation

Dr. Sara A. Courtneidge
contact affiliation	Oregon Health & Science University Department of Cell, Developmental & Cancer Biology 2720 S. Moody Avenue Portland, OR 97201 USA
contact email	courtneidge@ohsu.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
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/2021/01/PXD023867

PRIDE project URI

• PRIDE
  1. PXD023867
     1. Label: PRIDE project
     2. Name: Serine-threonine kinase TAO3 mediated trafficking of endosomes containing the invadopodia scaffold TKS5-alpha promotes cancer invasion and tumor growth