PXD020102-1

PXD020102 is an original dataset announced via ProteomeXchange.

Title	DOCK5 couples CDC42-GSK3 activation with focal adhesion morphogenesis to reinforce the establishment of polarity and promote YAP/TAZ activation during migration
Description	YAP and TAZ are transcriptional co-activators that are often constitutively active in triple negative breast cancer (TNBC) cells. But the mechanisms responsible for YAP/TAZ dysregulation in TNBC remain unclear. We hypothesized that RhoGEF activity in TNBC cells underpins YAP/TAZ activation in TNBC cells. Through systematic RNAi screening we found that the Focal Adhesion (FA) associated RhoGEF DOCK5 promotes YAP/TAZ nuclear translocation in proliferating TNBC cells. DOCK5 is required for 2D migration and 3D invasion, acting as a coincident detector that maintains cell polarity by stabilising GSK3 activation downstream of CDC42 at polarized leading edges only where FAs are being assembled. DOCK5 and CDC42 are required for cell survival and drug resistance in TNBC cells. Based on these studies we propose that cancer cell phenotypes such as drug resistance can be driven by cells adopting polarised, migratory shapes.
HostingRepository	PRIDE
AnnounceDate	2025-04-14
AnnouncementXML	Submission_2025-04-14_02:17:09.752.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	James Wright
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-29 07:32:18	ID requested
⏵ 1	2025-04-14 02:17:10	announced

Dataset with its publication pending

submitter keyword: LC-MSMS, Human, Cancer,TMT

Jyoti Choudhary
contact affiliation	The Institute of Cancer Research, London
contact email	jyoti.choudhary@icr.ac.uk
lab head
James Wright
contact affiliation	The Institute of Cancer Research
contact email	james.wright@icr.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020102
     1. Label: PRIDE project
     2. Name: DOCK5 couples CDC42-GSK3 activation with focal adhesion morphogenesis to reinforce the establishment of polarity and promote YAP/TAZ activation during migration