PXD037259

PXD037259 is an original dataset announced via ProteomeXchange.

Title	Targeting Lysine-Specific Demethylase 1 (KDM1A/LSD1) Impairs Colorectal Cancer Tumorigenesis by Affecting Cancer Cells Stemness, Motility and Differentiation
Description	Among all cancers, colorectal cancer (CRC) is the 3rd most common and the 2nd leading cause of death worldwide. New therapeutic strategies are required to target cancer stem cells (CSCs), a subset of tumor cells highly resistant to present-day therapy and responsible for tumor relapse. CSCs display dynamic genetic and epigenetic alterations that allow quick adaptations to perturbations. Lysine-specific histone demethylase 1A (KDM1A), a FAD-dependent H3K4me1/2 and H3K9me1/2 demethylase, was found to be upregulated in several tumors and associated with a poor prognosis due to its ability to maintain CSCs staminal features. Here, we explored the potential role of KDM1A targeting in CRC by characterizing the effect of KDM1A silencing in differentiated and CRC stem cells (CRC-SCs). In CRC primary samples, KDM1A expression was associated with a worse prognosis, confirming its role as an independent negative prognostic factor of CRC. Consistently, biological assays such as methylcellulose colony formation, invasion, and migration assays demonstrated a significantly decreased self-renewal potential, as well as migration and invasion potential upon KDM1A silencing. Our untargeted omics approach (transcriptomic and proteomic) revealed the association of KDM1A silencing with CRC-SCs cytoskeletal and metabolism remodeling towards a differentiated phenotype (e.g., the activation of a collateral mitochondrial metabolic pathway independent from succinate-CoA ligase GDP-forming subunit beta 2, expressions of brush border’s protein villin, and ketogenic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2) suggesting a key role of KDM1A in cell metabolism. Also, KDM1A silencing resulted in a 3-fold increase in the expression of miR-506-3p. Lastly, loss of KDM1A markedly reduced 53BP1 DNA repair foci, implying the involvement of KDM1A in the DNA damage response. Overall, our results indicate that KDM1A plays a key role in CRC progression and therefore it represents a promising epigenetic target to prevent tumor relapse.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:02:28.913.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	2022-10-10 07:52:55	ID requested
1	2023-07-20 10:42:32	announced
⏵ 2	2023-11-14 09:02:29	announced	2023-11-14: Updated project metadata.

Antona A, Leo G, Favero F, Varalda M, Venetucci J, Faletti S, Todaro M, Mazzucco E, Soligo E, Saglietti C, Stassi G, Manfredi M, Pelicci G, Cor, à D, Valente G, Capello D, Targeting lysine-specific demethylase 1 (KDM1A/LSD1) impairs colorectal cancer tumorigenesis by affecting cancer cells stemness, motility, and differentiation. Cell Death Discov, 9(1):201(2023) [pubmed]

submitter keyword: epigenome, KDM1A, tumor, proteome,CRC-SCs, LC-MS/MS

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, 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/2023/07/PXD037259

PRIDE project URI

• PRIDE
  1. PXD037259
     1. Label: PRIDE project
     2. Name: Targeting Lysine-Specific Demethylase 1 (KDM1A/LSD1) Impairs Colorectal Cancer Tumorigenesis by Affecting Cancer Cells Stemness, Motility and Differentiation