PXD043376

PXD043376 is an original dataset announced via ProteomeXchange.

Title	CdGAP is a Talin-binding protein and a target of TGF-β signaling that promotes HER2-positive breast cancer growth and metastasis
Description	Epithelial-to-mesenchymal transition (EMT) plays a crucial role in metastasis, which is the leading cause of death in breast cancer patients. We show that Cdc42 GTPase-activating protein (CdGAP) promotes tumor formation and metastasis to lungs in the HER2-positive (HER2+) murine breast cancer model. CdGAP facilitates intravasation, extravasation, and growth at metastatic sites. CdGAP depletion in HER2+ murine primary tumors mediates crosstalk with a Dlc1-RhoA pathway and is associated with a transforming growth factor-β (TGF-β)-induced EMT transcriptional signature. To further delineate the molecular mechanisms underlying the pro-migratory role of CdGAP in breast cancer cells, we searched for CdGAP interactors by performing a proteomic analysis using HEK293 cells overexpressing GFP-CdGAP. We found that CdGAP interacts with the adaptor Talin to modulate focal adhesion dynamics and integrin activation. Moreover, HER2+ breast cancer patients with high CdGAP mRNA expression combined with a high TGF-β-EMT signature are more likely to present lymph node invasion. Our results suggest CdGAP as a candidate therapeutic target for HER2+ metastatic breast cancer by inhibiting TGF-β and Integrin/Talin signaling pathways.
HostingRepository	PRIDE
AnnounceDate	2023-07-14
AnnouncementXML	Submission_2023-07-14_09:17:43.697.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	NathalieLamarche-Vane
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetic acid derivatized residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-28 14:34:01	ID requested
⏵ 1	2023-07-14 09:17:44	announced

Dataset with its publication pending

submitter keyword: HER2-positive breast cancer, EMT, Tumorigenesis, Cell invasion, TGF-β, Integrin, RhoGAP, Talin, Metastasis

NathalieLamarche-Vane
contact affiliation	Professor Research Institute-MUHC Cancer Research Program,Montreal
contact email	nathalie.lamarche@mcgill.ca
lab head
NathalieLamarche-Vane
contact affiliation	Department of Anatomy and Cell Biology, McGill University
contact email	nathalie.lamarche@mcgill.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043376
     1. Label: PRIDE project
     2. Name: CdGAP is a Talin-binding protein and a target of TGF-β signaling that promotes HER2-positive breast cancer growth and metastasis