ILF3 mediates lipid metabolism to promote pancreatic cancer development by regulating CPT1A-activated PPARa signaling pathway
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Xiaodong Huang
PROVIDER: PXD061949 | iProX | Tue Mar 18 00:00:00 GMT 2025
REPOSITORIES: iProX
Similar Datasets
Project description:Phospholipids containing polyunsaturated fatty acyl tails (PL-PUFAs) are susceptible to lipid peroxidation by reactive oxygen species, lipoxygenases, and radical species. The accumulation of peroxidized lipids in cell membranes overwhelms endogenous lipid repair processes and triggers ferroptosis. We discovered that phospholipids with both PUFA tails (PL-PUFA2s) acted as key drivers of ferroptosis in numerous cancer cell lines, compared with phospholipids with a single PUFA tail (PL-PUFA1s), which were substantially less capable of inducing ferroptosis. We found that exogenously supplied phosphatidylcholine with two PUFA tails (PC-PUFA2) was rapidly incorporated into and remodeled membranes in cell lipids. Moreover, PC-PUFA2s were enriched upon free PUFA treatment, suggesting a key role in driving free-PUFA-initiated ferroptosis. We examined the protein-binding profile of PC-PUFA2 and found a specific interaction with the mitochondrial electron transport chain complex I. We confirmed that PC-PUFA2s accumulate in mitochondria and induce production of mitochondrial ROS, which then spread to the endoplasmic reticulum. Depletion of mitochondria through mitophagy eliminated the enhanced potency of PC-PUFA2s over PC-PUFA1s in driving ferroptosis, consistent with mitochondria being the key target of PC-PUFA2s. PC-PUFA2s are thus important lipid markers and drivers of ferroptosis and may serve as future biomarkers and therapeutic targets for modulating ferroptosis in pathological contexts.
2025-05-06 | PXD041993 | Pride
Project description:Interleukin-1B (IL-1B) is pathologically activated by inflammasome-associated caspase-1 in rare autoinflammatory conditions and in wide-spread diseases. Therefore, IL-1B activity must be fine-tuned to enable anti-microbial responses whilst limiting collateral damage. Here we report that, relative to other inflammasome components, IL-1B is rapidly turned over by the proteasome and this correlates with its decoration by K11-, K63- and K48-linked ubiquitin chains. This IL-1 degradation signal is not only a feature of inflammasome priming but is also triggered upon inflammasome activation. We demonstrate that IL-1 K133 is modified by ubiquitin and forms a salt bridge with IL-1B D129. Loss of IL-1 K133 ubiquitylation, or disruption of the K133:D129 electrostatic interaction, stabilizes IL-1Bprotein levels. Accordingly, IL-1B K133R/K133R mice display increased precursor IL-1Bupon inflammasome priming and increased bioactive IL-1B following inflammasome activation, both in vitro and following LPS injection in vivo. These findings reveal new mechanisms for limiting IL-1B activity and safeguarding against damaging inflammation.
2021-04-01 | PXD021305 | Pride
Project description:We measured the effect of docetaxel treatment to three differentially responsive prostate cancer cell lines, LNCaP, DU145 and PC-3, based on a transcriptional time course response by microarray analysis. These cell lines represent both androgen independent (DU145 and PC-3) and androgen sensitive (LNCaP) cells
2016-07-21 | GSE83654 | GEO
Project description:We report here the broad transcriptomic program regulated by BACH2 transcription factor. We used a well suited in vitro model of B cell differentiation to evaluate transcriptomic program governed by BACH2 leading to Plasmocyte (PC) differentiation. In this model B cells were cultured with anti-BCR, CpG, CD40L and Interleukin-2 (IL2). This Interleukin triggers PC differentiation by directly repressing BACH2 expression. We artificially inhibit BACH2 expression by siRNA and found that this condition is sufficient to trigger PC differentiation without IL2. To understand global changes induced by enforced BACH2 downregulation we compared Chip-Sequencing data between activated B Cells and BACH2 deficient B cells (siBACH2). We found that BACH2 binds more than 3000 genes across the human genome. RNAsequencing comparing IL2 drivent committed cells and siBACH2 committed cells highlighs a large common trasncriptional program shared by both conditions and involved in B cell destiny. This study provides evidence that BACH2 is a guardian of B cell fate.
2017-08-29 | GSE102460 | GEO
Project description:Interleukin-17A (IL-17A) is a key mediator of protective immunity to yeast and bacterial infections but also drives the pathogenesis of several autoimmune diseases, such as psoriasis or psoriatic arthritis. Here, we show that the tetra-transmembrane protein CMTM4 is a subunit of the IL-17 receptor (IL-17R). CMTM4 constitutively associated with IL-17R subunit C (IL-17RC) to mediate its stability, posttranslational modification, and plasma membrane localization. Both mouse and human cell lines deficient in CMTM4 were largely unresponsive to IL-17A, due to their inability to assemble the IL-17 receptor signaling complex. Accordingly, CMTM4-deficient mice were largely resistant to experimental psoriasis. Collectively, our data identified CMTM4 as an essential component of the IL-17 receptor and a potential therapeutic target for treating IL-17-mediated autoimmune diseases.
2022-12-02 | PXD036366 | Pride
Project description:Proteomics of carboxylated polystyrene bead (1.0 um) phagosomes from murine bone marrow-derived macrophages. cells were either resting or treated with 100 U/ml IFN-γ (PeproTech) and 100 ng/ml LPS (Sigma) for 24 h, 20 ng/ml Interleukin-4 (IL4) (BD Pharmingen) for 48 h, 20 ng/ml Interleukin-13 (IL13), 10 ng/ml Interleukin-10 (IL10)for 48 h or Reprogrammed (IL4 was incubated with BMDMs for 24 h, and the medium was replaced with fresh medium containing IFN-γ/LPS to incubate for another 24 h). Phagosomes were isolated after 30 min bead inoculation.
2019-03-22 | PXD004520 | Pride
Project description:We report the application of paired Assay for Transposase-Accessible Chromatin (ATAC-seq) and RNA-seq data to profile the regulatory landscape and expression of 5 primary Plasma Cell (PC), 28 Multiple Myeloma (MM) PC as well as 5 cell lines samples. Findings discriminated MM and MM subgroup-specific changes such as the exclusive overexpression of CCND1 and CCND2 oncogenes. DNA accessibility changes were correlated to gene expression in a topologically constrained manner to elucidate novel enhancer - promoter interactions, genes and pathways critical for myeloma biology and developmentally activated or de novo formed enhancers. Additionally, the MM subgroup-specific TF network dependencies were studied to help identify prognostic markers. Finally, we discover and functionally validate the critical enhancer that regulates ectopic expression of CCND2 in MM.
2021-06-29 | GSE153379 | GEO
Project description:We report the application of paired Assay for Transposase-Accessible Chromatin (ATAC-seq) and RNA-seq data to profile the regulatory landscape and expression of 5 primary Plasma Cell (PC), 28 Multiple Myeloma (MM) PC as well as 5 cell lines samples. Findings discriminated MM and MM subgroup-specific changes such as the exclusive overexpression of CCND1 and CCND2 oncogenes. DNA accessibility changes were correlated to gene expression in a topologically constrained manner to elucidate novel enhancer - promoter interactions, genes and pathways critical for myeloma biology and developmentally activated or de novo formed enhancers. Additionally, the MM subgroup-specific TF network dependencies were studied to help identify prognostic markers. Finally, we discover and functionally validate the critical enhancer that regulates ectopic expression of CCND2 in MM.
2021-06-29 | GSE153380 | GEO
Project description:Phosphatidylcholine transfer protein (PC-TP, a.k.a StarD2) is abundantly expressed in liver and is regulated by PPARα. When fed the synthetic PPARα ligand fenofibrate, Pctp-/- mice exhibited altered lipid and glucose homeostasis. Microarray profiling of liver from fenofibrate fed wild type and Pctp-/- mice revealed differential expression of a broad array of metabolic genes, as well as their regulatory transcription factors. Because its expression controlled the transcriptional activities of both PPARα and HNF4α in cell culture, the broader impact of PC-TP on nutrient metabolism is most likely secondary to its role in fatty acid metabolism. 6 livers collected from PC-TP knockout mice fed a fenobrate-supplemented diet were used as the experimental group. 6 livers collected from wild type mice fed a fenofibrate-supplemented diet were used as the control group. RNA prepared from one liver was used to hybridize one GeneChip, so that there were 6 experimental GeneChips and 6 control GeneChips.
2010-08-12 | E-GEOD-17666 | biostudies-arrayexpress
Project description:Gastric adenocarcinoma (GAC) remains a significant cause of cancer-related deaths worldwide, with the majority of mortality resulting from metastatic spread. To elucidate the evolution of cancer cells and their interactions with the tumour microenvironment (TME), we conducted a comprehensive single-cell transcriptome and immune repertoire profiling of primary tumours (PRIs), matched liver metastases (LMs) or peritoneal carcinomatosis (PC), adjacent normal tissues, and blood samples from 20 treatment-naïve patients. We found that the TME within metastases varied substantially from PRIs and differed between LMs and PC samples. Indicative of immune evasion, we observed diminished T cell clonal expansion, a marked reduction in the fraction of tumour-reactive CD8 T cells, and an enrichment of naïve T cells, M2-like, and proliferative macrophages in PC samples compared to PRIs. LMs displayed significantly reduced B cells, with increased fractions of exhausted CD8 T cells and NK/NKT cells. Both LMs and PC showed nearly depleted plasma cells. Malignant cells largely exhibited diminished gastric lineage identity, predominantly adopting intestinal-like and mixed cell states, with the acquired expression of gastrointestinal stem-cell markers. LM cancer cells showed increased epithelial-to-mesenchymal signalling, while PC cancer cells had increased levels of aneuploidy. We observed differentially expressed cancer meta-programs and gene modules (GMs) between LMs and PC, with high GM2 expression in the PRI predicting an increased risk of distant metastases. Further analysis of GM signature genes revealed ferroptosis evasion through GPX4 upregulation during malignant progression. Functional validation via patient-derived xenografts and a novel autochthonous mouse model of GAC confirmed that genetic or pharmacological inhibition of ferroptosis resistance attenuates tumor growth and metastatic progression. Together, our mapping of malignant progression provides a rationale for targeting ferroptosis defense in combination with next-generation CAR T-cell immunotherapy as a potential avenue to overcome T cell dysfunction in advanced metastatic GAC therapy.
2024-05-23 | GSE239676 | GEO