PXD028708

PXD028708 is an original dataset announced via ProteomeXchange.

Title	Prolonged exposure to simulated microgravity promotes stemness impairing morphological, metabolic and migratory profile of pancreatic cancer cells: a comprehensive proteomic, lipidomic and trascriptomic analysis
Description	Gravitational biology and its effects on cancer cells are of great interest, especially today that space is more accessible than ever. Despite advances in space research, little is known about the impact of microgravity on tumor and its biology and data from the literature are often contradictory due to different setup, experimental designs and analyzed time-points. Exploiting the Random Positioning machine we evaluated on pancreatic cancer cells the effects of long-term exposure to simulated microgravity (SMG) performing a large proteomic, lipidomic and transcriptional analysis at 1, 7 and 9 days. Results indicate that SMG affects cellular morphology through a time-dependent activation of “Regulation of actin-based motility by Rho”and “Cdc42” pathways that contribute to the dynamic actin rearrangement involved in the formation of 3D spheroidal structures and in the enhancement of epithelial-to mesenchymal transition. To support energy stress remediation and counteract massive apoptosis activation and cell proliferation inhibition, induced by SMG, tumor cells downregulate the protein translational machinery, and undergo a metabolic reprogramming orchestrated by the activation of HIF-1a and PI3K/Akt pathways. These two pathways pave the way for glucose metabolism encouraging upregulation of glycolysis, mitochondrial activity, Tri-carboxylic acid cycle and fatty acid synthesis (rather than B oxidation), suggesting a de novo synthesis of triglycerides involved in the formation of membrane lipid bilayer and signaling mediators. This metabolic plasticity, typical of cancer stem cells, is in accordance with the SMG-mediated activation of PI3K/Akt/NFkB/ERK5/IL-8 signaling axis that significantly upregulates the expression of stem-associated proteins and expansion of cancer stem cells with a more mesenchymal phenotype and improved migratory capability. Altogether, our findings clearly indicate that microgravity induces cancer cell transformation towards the acquisition of cancer stem cell-like features, with a more aggressive and metastatic potential and pave the base for future study of response to anti neoplastic drugs under simulated microgravity.
HostingRepository	PRIDE
AnnounceDate	2022-05-19
AnnouncementXML	Submission_2022-05-19_13:31:53.265.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcello Manfredi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-22 12:36:48	ID requested
⏵ 1	2022-05-19 13:31:55	announced

Masini MA, Bonetto V, Manfredi M, Past, ò A, Barberis E, Timo S, Vanella VV, Robotti E, Masetto F, Andreoli F, Fiore A, Tavella S, Sica A, Donadelli M, Marengo E, Prolonged exposure to simulated microgravity promotes stemness impairing morphological, metabolic and migratory profile of pancreatic cancer cells: a comprehensive proteomic, lipidomic and transcriptomic analysis. Cell Mol Life Sci, 79(5):226(2022) [pubmed]

submitter keyword: Microgravity, Cancer stem cells, metabolism, proteomic, lipidomic

Marcello Manfredi
contact affiliation	Biological Mass Spectrometry Lab, Department of Translational Medicine (DiMeT),Center for Translational Research on Autoimmune & Allergic Diseases - CAAD, University of Piemonte Orientale Corso Trieste 15/A, 28100, Novara, Italy.
contact email	marcello.manfredi@uniupo.it
lab head
Marcello Manfredi
contact affiliation	University of Eastern Piedmont
contact email	marcello.manfredi@uniupo.it
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/2022/05/PXD028708

PRIDE project URI

• PRIDE
  1. PXD028708
     1. Label: PRIDE project
     2. Name: Prolonged exposure to simulated microgravity promotes stemness impairing morphological, metabolic and migratory profile of pancreatic cancer cells: a comprehensive proteomic, lipidomic and trascriptomic analysis