Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Phospholipase D2 suppresses tumor progression by regulation of IL-1β secretion from tumor-associated macrophages in bladder cancer microenvironment.

ABSTRACT: Phospholipase D2 suppresses tumor progression by regulation of IL-1β secretion from tumor-associated macrophages in bladder cancer microenvironment.

PROVIDER: PRJNA1132267 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Phospholipase D2 suppresses tumor progression by regulation of IL-1β secretion from tumor-associated macrophages in bladder cancer microenvironment.

Project description:The tumor microenvironment (TME) modulates therapeutic response and prognosis in patients with bladder cancer (BC). The roles of two phospholipase D (PLD) isoforms, PLD1 and PLD2 (hydrolysis of phosphatidylcholine to phosphatidic acid) in cancer cells have been well-studied in numerous cancer types, but their roles in the TME remain unclear. We used a mouse BC Pld2-knockout carcinogenesis model and global transcriptomic analysis to reveal that PLD2 was significantly involved in BC progression through immunosuppressive pathways in the TME. We therefore focused on PLD2 and tumor-associated macrophages (TAMs), which were increased in Pld2-knockout mice and further associated with poor prognoses in BC patients. In vitro, we found that Pld2- knockout mouse TAMs had significantly enhanced proliferation, correlating closely with increased IL-1β production. These results indicate that PLD2 suppresses BC progression by regulation of IL-1β secretion from TAMs in the TME, suggesting that PLD2 could serve as a potential therapeutic target for BC.

2024-09-01 | GSE271595 | GEO

Efferocytosis drives myeloid NLRP3 dependent inflammasome signaling and gasdermin D independent secretion of IL-1β to promote tumor growth

Project description:Caspase-1 signaling in myeloid suppressor cells can promote T-cell independent cancer progression, but the regulation of inflammasome signaling within the highly heterogeneous myeloid cells in the tumor milieu remains elusive. To resolve this complexity, scRNA-seq of human head & neck carcinoma identified distinct inflammasome complex genes within specific clusters of tumor-infiltrating myeloid cells. Among these myeloid cells, NLRP3 sensor and downstream effector IL-1β transcripts were enriched in multiple monocytic and macrophage subtypes in the TME. In vivo, we showed that NLRP3, and not AIM2, phenocopied the caspase-1/IL-1β dependent tumor progression. Paradoxically, we found that myeloid-intrinsic caspase-1 signaling within the TME increased myeloid survival without significant intratumoral trafficking as would be predicted from their canonical pyroptotic function. Mechanistically, this myeloid NLRP3/IL-1β signaling axis promotion of tumor growth was found to be gasdermin D independent. When we probed for the tumor intrinsic factors that regulated NLRP3/IL-1β signaling, we found that mononuclear phagocyte-mediated efferocytosis of dying tumor cells in the TME directly activated NLRP3 dependent inflammasome signaling to drive IL-1β secretion and to promote tumor growth. Dynamic RNA velocity analysis of the single cell transcriptomic dataset showed a strong directional flow from efferocytosis gene-sethigh macrophages to an inflammasome gene-sethigh macrophage population. Cumulatively, we provide a novel inflammasome signaling axis between tumor apoptosis and myeloid cells that characterizes chronic inflammation induced malignancy.

2022-04-13 | GSE200560 | GEO

Genome-wide analysis expression of ileum tumor samples from FVBN/APCmin and iPGC-1β/APCmin

Project description:Analysis of metabolic pathway gene expression. The hypothesis tested in the present study is to assess mRNA level changes in metabolic genes in intestinal tumors from APCmin mice overexpressing PGC-1β specifically in the intestine. Total RNA obtained from ileum tumor samples from iPGC-1β/APCmin mice was compared to the total RNA extracted from FVBN/APCmin mice.

2015-03-01 | E-GEOD-61642 | biostudies-arrayexpress

Pancreatic Tumor Microenvironment Maintains Tumor Growth through Nucleosides Secretion

Project description:Pancreatic Tumor Microenvironment Maintains Tumor Growth through Nucleosides Secretion

| PRJNA770663 | ENA

Efferocytosis drives myeloid NLRP3 dependent inflammasome signaling and gasdermin D independent secretion of IL-1β to promote tumor growth

Project description:Efferocytosis drives myeloid NLRP3 dependent inflammasome signaling and gasdermin D independent secretion of IL-1β to promote tumor growth

| PRJNA825271 | ENA

Gasdermin D mediates host cell death but not interleukin-1β secretion in Mycobacterium tuberculosis infected macrophages

Project description:Necrotic cell death represents a major pathogenic mechanism of Mycobacterium tuberculosis (Mtb) infection. It is increasingly evident that Mtb induces several types of regulated necrosis but how these are interconnected and linked to the release of pro-inflammatory cytokines remains unknown. Exploiting a clinical cohort of tuberculosis patients, we show here that the number and size of necrotic lesions correlates with IL-1β plasma levels as a strong indicator of inflammasome activation. Our mechanistic studies reveal that Mtb triggers mitochondrial permeability transition (mPT) and subsequently extensive macrophage necrosis which requires activation of the NLRP3 inflammasome. NLRP3 driven mitochondrial damage is dependent on proteolytic activation of the pore forming effector protein gasdermin D (GSDMD) which links two distinct cell death machineries. Intriguingly, GSDMD, but not the membranolytic mycobacterial ESX-1 secretion system is dispensable for IL-1β secretion from Mtb-infected macrophages. Thus, our study dissects a novel mechanism of pathogen induced regulated necrosis by identifying mitochondria as central regulatory hubs capable of delineating cytokine secretion and lytic cell death.

2022-02-17 | PXD029017 | Pride

Pseudoalteromonas tunicata D2 strain:D2

Project description:Pseudoalteromonas tunicata D2 strain:D2 Genome sequencing

| PRJNA196226 | ENA

Arthrobacter sp. D2 strain:D2

Project description:Arthrobacter sp. D2 strain:D2 Genome sequencing and assembly

| PRJNA314012 | ENA

IL-1β induces the rapid secretion of the antimicrobial protein IL-26 from Th17 cells

Project description:IL-1β induces the rapid secretion of the antimicrobial protein IL-26 from Th17 cells

| PRJNA524825 | ENA

Kocuria rhizophila strain:D2 | isolate:D2

Project description:Kocuria rhizophila strain:D2 | isolate:D2 Genome sequencing and assembly