Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tumor ENPP1(CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer [shENPP]

ABSTRACT: Locoregional failure (LRF) in breast cancer patients post-surgery and post-irradiation (IR) is linked to a dismal prognosis. In a refined new model, we identified Enpp1 (Ectonucleotide pyrophosphatase /phosphodiesterase 1/CD203a) to be closely associated with LRF. Enpp1high circulating tumor cells (CTC) contribute to relapse by a self-seeding mechanism. This process requires the infiltration of PMN-MDSC and neutrophil extracellular traps (NET) formation. Genetic and pharmacological Enpp1 inhibition or NET blockade extend relapse-free survival. Furthermore, in combination with fractionated irradiation (FD), Enpp1 abrogation obliterates LRF.

ORGANISM(S): Mus musculus

PROVIDER: GSE193690 | GEO | 2022/01/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Tumor ENPP1(CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer [oeENPP]

2022-01-17 | GSE193689 | GEO

Tumor ENPP1(CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer [array]

Project description:Locoregional failure (LRF) in breast cancer patients post-surgery and post-irradiation (IR) is linked to a dismal prognosis. In a refined new model, we identified Enpp1 (Ectonucleotide pyrophosphatase /phosphodiesterase 1/CD203a) to be closely associated with LRF. Enpp1high circulating tumor cells (CTC) contribute to relapse by a self-seeding mechanism. This process requires the infiltration of PMN-MDSC and neutrophil extracellular traps (NET) formation. Genetic and pharmacological Enpp1 inhibition or NET blockade extend relapse-free survival. Furthermore, in combination with fractionated irradiation (FD), Enpp1 abrogation obliterates LRF. Mechanistically, Enpp1-generated adenosinergic metabolites enhance Haptoglobin (Hp) expression. This inflammatory mediator elicits myeloid invasiveness and promotes NET formation. Accordingly, a significant increase in ENPP1 and NET formation is detected in relapsed human breast cancer tumors. Moreover, high ENPP1 or HP levels are associated with poor prognosis. These findings unveil the ENPP1/HP axis as an unanticipated mechanism exploited by tumor cells linking inflammation to immune remodeling favoring local relapse.

2022-01-17 | GSE193691 | GEO

ENPP1

Project description:Oryctolagus cuniculus ENPP1, Oryctolagus cuniculus ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), mRNA. [Source:RefSeq mRNA;Acc:NM_001082742], is expressed in 1 baseline experiment(s);

| ENSOCUG00000014455 | ExpressionAtlas

Oral ENPP1 inhibitor designed using generative AI as next generation STING modulator for solid tumorse solid tumors

Project description:NCOMMS-24-54326: Despite the STING-type-I interferon pathway playing a key role in effective anti-tumor immunity, the therapeutic benefit of direct STING agonists appears limited. In this study, we used several artificial intelligence techniques and patient-based multi-omic data to show that Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1), which hydrolyzes STING-activating cyclic GMP-AMP (cGAMP), is a safer and more effective STING-modulating target than direct STING agonism in multiple solid tumors. We then leveraged our generative chemistry artificial intelligence-based drug design platform to facilitate the design of ISM5939, an orally bioavailable ENPP1-selective inhibitor capable of stabilizing extracellular cGAMP and activating bystander antigen-presenting cells without inducing either toxic inflammatory cytokine release or tumor-infiltrating T-cell death. In murine syngeneic models across cancer types, ISM5939 synergizes with targeting the PD-1/PD-L1 axis and genotoxic chemotherapy in suppressing tumor growth with good tolerance. Our findings provide new evidence supporting ENPP1 as a novel innate immune checkpoint across solid tumors and reports the first AI design-aided ENPP1 inhibitor, ISM5939, as a cutting-edge STING modulator for cancer therapy, paving a new path for immunotherapy advancements.

2025-04-13 | GSE277788 | GEO

ENPP1

Project description:Monodelphis domestica ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1 [Source:NCBI gene;Acc:100031043], is expressed in 2 baseline experiment(s);

| ENSMODG00000017564 | ExpressionAtlas

Enpp1

Project description:Rattus norvegicus Enpp1, ectonucleotide pyrophosphatase/phosphodiesterase 1 [Source:RGD Symbol;Acc:628825], is differentially expressed in 33 experiment(s);

| ENSRNOG00000013994 | ExpressionAtlas

Enpp1

Project description:Rattus norvegicus Enpp1, ectonucleotide pyrophosphatase/phosphodiesterase 1 [Source:RGD Symbol;Acc:628825], is expressed in 5 baseline experiment(s);

| ENSRNOG00000013994 | ExpressionAtlas

ENPP1

Project description:Sus scrofa ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1 [Source:VGNC Symbol;Acc:VGNC:87708], is differentially expressed in 4 experiment(s);

| ENSSSCG00000004193 | ExpressionAtlas

ENPP1

Project description:Sus scrofa ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1 [Source:VGNC Symbol;Acc:VGNC:87708], is expressed in 6 baseline experiment(s);

| ENSSSCG00000004193 | ExpressionAtlas

ENPP1

Project description:Macaca mulatta ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1 [Source:VGNC Symbol;Acc:VGNC:72222], is expressed in 2 baseline experiment(s);

| ENSMMUG00000014151 | ExpressionAtlas

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data