PXD015152 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-08-25 23:56:28 | ID requested | |
⏵ 1 | 2022-02-15 09:31:26 | announced | |
Publication List
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] |
Keyword List
curator keyword: Biomedical |
submitter keyword: leukemia, human, Asparagine |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD015152
- Label: PRIDE project
- Name: Identification of critical therapeutic nodes to overcome Asparagine deprivation resistance in melanoma