Dataset Information

MYC deregulation sensitizes cancer cells to N-myristoyltransferase inhibition - DoHH2 proteomics

ABSTRACT: Human N-myristoyltransferases (NMTs) catalyze N-terminal protein N-myristoylation and are promising targets in cancer, with an emerging mechanistic rationale for targeted therapy. Here, we screened 245 cancer cell lines against IMP-1320, a potent NMT inhibitor (NMTi), and conducted pathway-level analyses to identify that deregulated MYC increases cancer cell sensitivity to NMTi. Proteomics on detergent-enriched membrane fractions in MYC or MYCN-deregulated cancer cell models revealed that cell death is associated at least in part with loss of membrane association of mitochondrial respiratory complex I. This is concurrent with loss of myristoylation and degradation of the complex I assembly factor NDUFAF4, and induction of mitochondrial dysfunction, driven by MYC or MYCN-deregulation. NMTi eliminated or suppressed MYC and MYCN-driven tumors in vivo without overt toxicity, suggesting that this constitutive co-translational protein modification can be targeted in MYC-driven cancers. This dataset comprises the proteomic data obtained from DoHH2 tumours, excised from CB17/SCID mice treated intraperitoneally with vehicle or IMP1320 (25 mg/kg/day), on a three days on/three days off dosing schedule.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell

DISEASE(S): Lymphoma

SUBMITTER: Wouter Kallemeijn

LAB HEAD: Professor Dr. Edward W. Tate

PROVIDER: PXD063851 | Pride | 2025-07-30

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	JH-WK-DDOH2-250-1_S3-A1_1_11792.d.zip	Other
	JH-WK-DDOH2-250-2_S3-A2_1_11793.d.zip	Other
	JH-WK-DDOH2-250-3_S3-A3_1_11794.d.zip	Other
	JH-WK-DDOH2-250-4_S3-A4_1_11795.d.zip	Other
	JH-WK-DDOH2-250-5_S3-A5_1_11796.d.zip	Other

Items per page:

1 - 5 of 9

Similar Datasets

Project description:Desmoplastic small round cell tumor (DSRCT) is a highly aggressive cancer predominantly occurring in young male adolescents. It mainly arises at sites lined by mesothelium, such as the abdominal cavity, and is driven by the pathognomonic EWSR1::WT1 fusion oncoprotein. The dismal survival rates (5–20%) have not significantly improved since its first description in 1989, also due to a lack of comprehensive datasets that could shed new light on the biology of the disease and uncover novel diagnostic markers and therapeutic targets. Thus, we established genome-wide single-cell RNA-sequencing and bulk proteomic data of in vitro and in vivo-generated EWSR1::WT1 knockdown models and combined them with an original systems-biology-based pipeline including patient data, resulting in a rich resource for discovery analyses. This approach revealed the alpha-2/delta subunit of the voltage-dependent calcium channel complex, CACNA2D2, as a strongly overexpressed direct target of EWSR1::WT1 in DSRCTs, which is regulated by an EWSR1::WT1-bound super-enhancer. Ectopic expression of the main EWSR1::WT1 isoforms in mesothelial cells, the putative cell of origin of DSRCTs, confirmed that EWSR1::WT1 is sufficient to induce super-enhancer formation at the CACNA2D2 locus followed by robust transcription of this gene. Moreover, single-cell and bulk-level analyses on patient samples and cell line-derived xenografts highlighted CACNA2D2 as a critical mediator of the EWSR1::WT1 oncogenic signature. Based on bulk and single-cell transcriptomic data, the computed CACNA2D2 signature could be further utilized to robustly identify DSRCTs in reference sets. Finally, we show that CACNA2D2 is a highly sensitive and specific single biomarker for fast, simple, and cost-efficient diagnosis of DSRCT. Collectively, we established a freely available large-scale multi-omics dataset for this devastating disease and provide a blueprint of how such data can be used to identify a new and clinically relevant diagnostic marker, which may significantly reduce misdiagnoses, and thus improve patient care.

Dataset Information

MYC deregulation sensitizes cancer cells to N-myristoyltransferase inhibition - DoHH2 proteomics

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets