PXD048091

PXD048091 is an original dataset announced via ProteomeXchange.

Title	Tumor cells express and maintain HMGB1 in the reduced isoform to enhance CXCR4-mediated migration
Description	During inflammation and tissue regeneration, the alarmin High Mobility Group Box 1 (HMGB1), in its reduced isoform, enhances the activity of the chemokine CXCL12, forming a heterocomplex that acts via the chemokine receptor CXCR4. Despite the established roles of both HMGB1 and CXCL12 in tumor progression and metastatic spread to distal sites, the role of the CXCL12/HMGB1 heterocomplex in cancer has never been investigated. By employing a newly established mass spectrometry protocol that allows an unambiguous distinction between reduced (red HMGB1) and oxidized (ox HMGB1) HMGB1 isoforms in cell lysates, we demonstrate that human epithelial cells derived from breast (MCF-7 and MDA-MB-231) and prostate (PC-3) cancer predominantly express red-HMGB1, while primary CD3+ T lymphocytes from peripheral blood express both HMGB1 isoforms. All these cancer cells release HMGB1 in the extracellular microenvironment together with varying concentrations of thioredoxin and thioredoxin reductase. The CXCL12/HMGB1 heterocomplex enhances, via CXCR4, the directional migration and invasiveness of cancer cells characterized by high metastatic potential that possess a fully active thioredoxin system, contributing to maintain red-HMGB1. On the contrary, cancer cells with low metastatic potential, lack thioredoxin reductase, promptly uptake CXCL12 and fail to respond to the heterocomplex. Our study demonstrates that the responsiveness of cancer cells to the CXCL12/HMGB1 heterocomplex, resulting in enhanced cell migration and invasiveness, depends on the maintenance of HMGB1 in its reduced isoform, and suggests disruption of the heterocomplex as a potential therapeutic target to inhibit invasion and metastatic spread in cancer therapies.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:37:57.207.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matteo Pecoraro
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-22 15:45:52	ID requested
1	2024-05-02 06:12:49	announced
⏵ 2	2024-10-22 06:37:57	announced	2024-10-22: Updated project metadata.

10.3389/FIMMU.2024.1358800;

submitter keyword: breast cancer, thioredoxin, heterocomplex,CXCL12, HMGB1, prostate cancer

Mariagrazia Uguccioni
contact affiliation	Institute for Research in Biomedicine, Università della Svizzera italiana, Via Chiesa 5, 6500 Bellinzona, Switzerland
contact email	mariagrazia.uguccioni@irb.usi.ch
lab head
Matteo Pecoraro
contact affiliation	Institute for Research in Biomedicine, Via Francesco Chiesa 5 - CH-6500 Bellinzona
contact email	matteo.pecoraro@irb.usi.ch
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/2024/05/PXD048091

PRIDE project URI

• PRIDE
  1. PXD048091
     1. Label: PRIDE project
     2. Name: Tumor cells express and maintain HMGB1 in the reduced isoform to enhance CXCR4-mediated migration