PXD015152

PXD015152 is an original dataset announced via ProteomeXchange.

Title	Identification of critical therapeutic nodes to overcome Asparagine deprivation resistance in melanoma
Description	Asparagine deprivation by L-Asparaginase is a successful therapeutic strategy in Acute Lymphoblastic Leukemia, with resistance occurring due to upregulation of ASNS. L-Asparaginase efficacy in solid tumors is hampered by dose-related toxicities. Large scale loss of function genetic screens identified ASNS, the only human enzyme synthetizing asparagine, as a cancer dependency in several solid malignancies, including melanoma. We here evaluate the therapeutic potential of targeting ASNS in melanoma cells in-vitro and in-vivo. Using ex-vivo quantitative proteome and transcriptome profiling, we observed that concomitant ASNS deletion and asparagine deprivation elicit a compensatory mechanism allowing tumor growth. Genome wide CRISPR screens upon manipulation of aminoacid levels identifies MAPK and GCN2 as critical nodes mediating the observed resistance mechanism. Importantly MEK and GCN2 inhibitor synergize with L-Asparaginase suggesting novel potential therapeutic strategy in melanoma.
HostingRepository	PRIDE
AnnounceDate	2022-02-15
AnnouncementXML	Submission_2022-02-15_09:31:25.524.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Debora Bonenfant
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-25 23:56:28	ID requested
⏵ 1	2022-02-15 09:31:26	announced

Apfel V, Begue D, Cordo' V, Holzer L, Martinuzzi L, Buhles A, Kerr G, Barbosa I, Naumann U, Piquet M, Ruddy D, Weiss A, Ferretti S, Almeida R, Bonenfant D, Tordella L, Galli GG, Therapeutic Assessment of Targeting ASNS Combined with l-Asparaginase Treatment in Solid Tumors and Investigation of Resistance Mechanisms. ACS Pharmacol Transl Sci, 4(1):327-337(2021) [pubmed]

curator keyword: Biomedical

submitter keyword: leukemia, human, Asparagine

Debora Bonenfant
contact affiliation	Debora Bonenfant, Novartis Institutes for Biomedical Research, Basel, Switzerland
contact email	debora.bonenfant@novartis.com
lab head
Debora Bonenfant
contact affiliation	Novartis Institutes for BioMedical Research
contact email	debora.bonenfant@novartis.com
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/2022/02/PXD015152

PRIDE project URI

• PRIDE
  1. PXD015152
     1. Label: PRIDE project
     2. Name: Identification of critical therapeutic nodes to overcome Asparagine deprivation resistance in melanoma