PXD045777

PXD045777 is an original dataset announced via ProteomeXchange.

Title	Multilevel Plasticity and Altered Glycosylation Drive Aggressiveness in Hypoxic and Glucose-Deprived Bladder Cancer Cells
Description	Bladder tumours with aggressive characteristics often inhabit microenvironmental niches marked by low oxygen levels (hypoxia) and limited glucose supply due to inadequate vascularization. The molecular mechanisms facilitating cellular adaptation to these stimuli remain largely elusive. Employing a multi-omics approach, we discovered that hypoxic and glucose-deprived cancer cells enter a quiescent state supported by mitophagy, fatty acid β-oxidation, and amino acid catabolism, concurrently enhancing their invasive capabilities remarkably. Reoxygenation and glucose restoration efficiently reversed cell dormancy without affecting cellular viability, highlighting significant molecular plasticity in adapting to microenvironmental cues. Furthermore, cancer cells exhibited substantial perturbation of protein O-glycosylation, leading to simplified glycophenotypes with shorter glycosidic chains. Exploiting glycoengineered cell models, we established that immature glycosylation contributes to reduced cell proliferation and increased invasion. Our findings collectively indicate that hypoxia and glucose deprivation trigger cancer aggressiveness, reflecting an adaptive escape mechanism underpinned by altered metabolism and protein glycosylation. Building on these data, we have performed on a phosphoproteomics characterization of hypoxic and glucose-deprived bladder cancer cell lines, aiming to gain a deeper understanding of the signaling rewiring experienced by cancer cells under microenvironmental stress and to identify potential targets for future clinical intervention.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:34:43.540.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tim Veth
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-28 07:18:09	ID requested
1	2024-03-26 22:07:23	announced
⏵ 2	2024-10-22 06:34:43	announced	2024-10-22: Updated project metadata.

10.1101/2023.10.21.561355;

submitter keyword: glucose deprivation

molecular plasticity

multiomics

phosphoproteomics,Hypoxia, cancer microenvironment

José Alexandre Ferreira
contact affiliation	Portuguese Institute of Oncology of Porto
contact email	jose.a.ferreira@ipoporto.min-saude.pt
lab head
Tim Veth
contact affiliation	Utrecht University
contact email	t.s.veth@uu.nl
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/2024/03/PXD045777

PRIDE project URI

• PRIDE
  1. PXD045777
     1. Label: PRIDE project
     2. Name: Multilevel Plasticity and Altered Glycosylation Drive Aggressiveness in Hypoxic and Glucose-Deprived Bladder Cancer Cells