PXD039351

PXD039351 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	DOCK8 is a Novel Regulator of Lysosome Mediated Pancreatic Cancer Invasion
Description	Amplified lysosome activity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) orchestrated by oncogenic KRAS that mediates tumor progression and metastasis, though the mechanisms underlying this phenomenon remain unclear. Using comparative proteomics, we found that oncogenic KRAS significantly enriches levels of the guanine nucleotide exchange factor (GEF) DOCK8 on lysosomes. Surprisingly, we found that DOCK8 is aberrantly expressed in a subset of PDAC where it promotes cell invasion and proliferation. Further, DOCK8 associates with lysosomes and regulates lysosomal morphology and motility. DOCK8 promotes actin polymerization at the surface of lysosomes, while increasing the levels and proteolytic activity of the lysosomal protease cathepsin B. Depletion of DOCK8 significantly reduces extracellular matrix degradation and impairs the invasive capacity of PDAC cells. Further, CRISPR-based knockout of DOCK8 dramatically reduces tumor size and metastasis in vivo. Together, these findings implicate ectopic expression of DOCK8 as a key driver of KRAS-driven lysosomal regulation, tumor progression, and metastasis.
HostingRepository	MassIVE
AnnounceDate	2023-08-25
AnnouncementXML	Submission_2023-08-25_11:27:35.135.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Carrie Jo Heppelmann
SpeciesList	scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList	Carbamidomethyl; Oxidation; Acetyl
Instrument	Q Exactive

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-10 09:25:28	ID requested
⏵ 1	2023-08-25 11:27:35	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: Metastasis, invasion, pancreatic cancer, lysosome, matrix degradation

submitter keyword: Metastasis, invasion, pancreatic cancer, lysosome, matrix degradation

Contact List

Gina L Razidlo
contact affiliation	Mayo Clinic
contact email	razidlo.gina@mayo.edu
lab head
Carrie Jo Heppelmann
contact affiliation	Mayo Clinic
contact email	holtzheppelmann.carrie@mayo.edu
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset URI

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://massive.ucsd.edu/MSV000091036/