PXD014506-1

PXD014506 is an original dataset announced via ProteomeXchange.

Title	Chemotaxis in pancreatic ductal adenocarcinoma metastasis: An unexpected role of N-WASP in response of cells to self-generated gradients and LPA receptor trafficking
Description	Pancreatic ductal adenocarcinoma is one of the most invasive and metastatic cancers and has a dismal 5-year survival rate. Here we show that N-WASP is required for the metastatic process, with roles in both chemotaxis, steering cells out of primary tumours, and matrix remodelling, allowing them to escape. Lysophosphatidic acid, a signalling lipid abundant in blood and ascites fluid, is both a mitogen and chemoattractant for PDAC cells. Pancreatic cancer cells efficiently break LPA down as they respond to it, setting up a self-generated gradient that directs cells out of the tumour. N-WASP depleted cells are unable to respond to LPA gradients and show altered RhoA activation, leading to a loss of cell contractility and traction forces, and reduced metastasis in vitro and in vivo. N-WASP couples LPA receptor signalling to RhoA via the endocytic adapter SNX18, and promotes sensitivity by preventing receptor degradation and promoting recycling of the LPA receptor back to the cell surface. Coordinated by N-WASP, the LPA-LPAR signalling loop promotes RhoA-mediated contractility and force generation. Perturbing this pathway chemically, or by CRISPR deletion severely impairs invasion through complex 3D environments or peritoneal explants, and impairs remodelling of fibrillar collagen. We thus reveal N-WASP as a central controller of a chemotactic loop between PDAC cells and microenvironmental conditions that drives metastasis.
HostingRepository	PRIDE
AnnounceDate	2020-03-06
AnnouncementXML	Submission_2020-03-06_04:53:39.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sergio Lilla
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-05 08:55:20	ID requested
⏵ 1	2020-03-06 04:53:40	announced
2	2024-10-22 04:03:47	announced	2024-10-22: Updated project metadata.

Juin A, Spence HJ, Martin KJ, McGhee E, Neilson M, Cutiongco MFA, Gadegaard N, Mackay G, Fort L, Lilla S, Kalna G, Thomason P, Koh YWH, Norman JC, Insall RH, Machesky LM, N-WASP Control of LPAR1 Trafficking Establishes Response to Self-Generated LPA Gradients to Promote Pancreatic Cancer Cell Metastasis. Dev Cell, 51(4):431-445.e7(2019) [pubmed]

submitter keyword: Pancreatic cancer metastasis, cancer invasion, chemotaxis, cancer cell signalling, cell migration, receptor trafficking

Sara Rossana Zanivan
contact affiliation	CRUK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK.
contact email	s.zanivan@beatson.gla.ac.uk
lab head
Sergio Lilla
contact affiliation	Proteomics
contact email	s.lilla@beatson.gla.ac.uk
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/2020/03/PXD014506

PRIDE project URI

• PRIDE
  1. PXD014506
     1. Label: PRIDE project
     2. Name: Chemotaxis in pancreatic ductal adenocarcinoma metastasis: An unexpected role of N-WASP in response of cells to self-generated gradients and LPA receptor trafficking