PXD003316-3

PXD003316 is an original dataset announced via ProteomeXchange.

Title	Tumor matrix stiffness induces CCN1/CYR61 upregulation of N-Cadherin to promote cancer cell trans-endothelial migration and metastasis
Description	Tumor progression is often accompanied with increased extracellular matrix stiffness, but how this affects endothelial cells (ECs) is largely unknown. We used mass spectrometry to analyse the proteomic changes of primary human ECs cultured on physiological or tumor stiffness and found that CCN1/CYR61 is highly induced by tumor stiffness. Knock out of Ccn1 in the vasculature of Ccn1loxP/loxP mice by administrating a soluble form of Cre shows that fewer of the treated mice harbour circulating tumor cells and lung metastases, without affecting primary tumor growth, using the B16F10 syngeneic mouse melanoma model This demonstrates that CCN1 loss in the host impairs cancer metastasis and we dissected the molecular mechanism in vitro. Stiffness-induced CCN1 acts via (integrin αvβ3), FAK, beta-catenin signalling to increase N-Cadherin expression in ECs, which, in turn, leads to an elevated adhesion of cancer cells to ECs via N-Cadherin homophilic interactions.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:27:02.057.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sara Zanivan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-12-10 01:05:03	ID requested
1	2017-07-07 06:54:00	announced
2	2017-07-17 06:36:19	announced	Updated publication reference for PubMed record(s): 28694244.
⏵ 3	2024-10-22 04:27:04	announced	2024-10-22: Updated project metadata.

Reid SE, Kay EJ, Neilson LJ, Henze AT, Serneels J, McGhee EJ, Dhayade S, Nixon C, Mackey JB, Santi A, Swaminathan K, Athineos D, Papalazarou V, Patella F, Rom, á, n-Fern, á, ndez Á, ElMaghloob Y, Hernandez-Fernaud JR, Adams RH, Ismail S, Bryant DM, Salmeron-Sanchez M, Machesky LM, Carlin LM, Blyth K, Mazzone M, Zanivan S, Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO J, 36(16):2373-2389(2017) [pubmed]

10.15252/embj.201694912;

curator keyword: Biomedical

submitter keyword: stiffness

protome

SILAC

CCN1

Matrigel

HUVEC

tumour

vasculature

Sara Zanivan
contact affiliation	CRUK Beatson Institute
contact email	s.zanivan@beatson.gla.ac.uk
lab head
Sara Zanivan
contact affiliation	Tumour Microenvironment & Proteomics
contact email	s.zanivan@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/2017/07/PXD003316

PRIDE project URI

• PRIDE
  1. PXD003316
     1. Label: PRIDE project
     2. Name: Tumor matrix stiffness induces CCN1/CYR61 upregulation of N-Cadherin to promote cancer cell trans-endothelial migration and metastasis