OVs cytotoxic effort for bladder cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Zhiping Wang
PROVIDER: PXD056114 | iProX | Sat Sep 21 00:00:00 BST 2024
REPOSITORIES: iProX
Similar Datasets
Project description:It is widely acknowledged that gasdermin family proteins, which are known as the executors of pyroptosis, undergo protease-mediated cleavage prior to inducing pyroptosis. Here, we unexpectedly discovered a non-canonical form of pyroptosis mediated by full-length GSDME (FL-GSDME) without any proteolytic cleavage. Upon intense ultraviolet (UV) irradiation-triggered DNA damage, hyperactivation of nuclear PARP1 led to extensive formation of poly(ADP-ribose) (PAR) polymers and then release to the cytoplasm.These PAR polymers activate PARP5 to catalyze GSDME PARylation, resulted in a conformational change in GSDME that relieved autoinhibition imposed by its C terminus on the N terminus. On the other hand, intense UV irradiation boosted mitochondrial fission-dependent generation of mitochondrial reactive oxygen species (mito-ROS), further promoting cytochrome c-catalyzed peroxidation of cardiolipin. This lipid-ROS signal was then sensed by PARylated-GSDME and then induced oxidative oligomerization of GSDME, which facilitated FL-GSDME plasma membrane targeting for perforation, eventually inducing pyroptosis. Reagents that concurrently stimulate PARPs activity and lipid-ROS also induced sequential modifications i.e., PARylation and oxidation of FL-GSDME and synergistically promoted pyroptotic cell death. Overall, our findings elucidate a novel mechanism underlying cleavage-independent function of GSDME in executing cell demise, further enriching the paradigms and cognition of FL-GSDME-mediated non-canonical pyroptosis.
2024-06-17 | PXD051840 | Pride
Project description:Pyroptosis is an emerging programmed cell death with great potential in antitumor immunotherapy. However, the actual application of pyroptosis is hampered by its nonspecificity and inefficiency. In this study, a reactive oxygen species (ROS) responsive potassium (K+) ionophore-based nanoplatform rPPAA18C6 is constructed based on the triblock polymers PEG-PPBAEM-PAA18C6 to potentiate cancer pyroptosis and immunotherapy via the K+ metabolic disturbance mediated endoplasmic reticulum (ER) stress. The PEG (P) is used to prolong the circulation time in vivo, PPBAEM (r) is used to target the tumor cells and responds to the higher ROS, and PAA18C6 is used to perturb of K+ homeostasis. Moreover, rPPAA18C6 can also function as a drug carrier for chemodrug (doxorubicin, Dox). We find that rPPAA18C6@Dox provokes immune responses in melanoma (B16F10) via pyroptosis-related immunogenic cell death (ICD), in which damage-associated molecular patterns (DAMPs) are released to promote maturation of dendritic cells (DCs), activate cytotoxic T lymphocytes (CTLs), and convert immunosuppressive “cold” tumor to immunogenic “hot” tumor. Moreover, the combined therapy with anti-PD-L1 exhibits apparent tumor suppression far more than expected, suggesting a powerful candidate of rPPAA18C6@Dox for high-efficient immune checkpoint blockade (ICB) therapy. This study thus provides a promising strategy to specifically initiate pyroptosis and potentiate immunotherapy by perturbation of K+ metabolism via a smart nanoplatform.
2025-01-01 | GSE256169 | GEO
Project description:An unmet challenge in managing breast cancer is treatment failure due to resistance to apoptosis-inducing chemotherapies. Thus, it is important to identify novel non-apoptotic therapeutic agents. Several non-apoptotic programmed cell death pathways utilize specific cellular signaling events to trigger lytic and pro-inflammatory cell death. PANoptosis, which encompasses pyroptosis, apoptosis and necroptosis, is of paramount importance in the regulation of cell death and immune responses. Our study illustrates that ophiobolin A (OpA) is an anti-cancer agent that triggers lytic cell death in breast cancer cells, including triple-negative breast cancer (TNBC), via a mechanism dependent on RIPK1. This study reveals that OpA induces typical pyroptosis-like characteristics, including cellular swelling, plasma membrane rupture, GSDMD cleavage and release of cytokines in breast cancer cells. The involvement of caspase 3, RIPK1, and GSDMD suggests that PANoptosis is activated upon OpA treatment in breast cancer. The induction of pro-inflammatory cell death suggests potential applications for OpA in cancer treatment.
2024-09-17 | GSE277026 | GEO
Project description:Ferroptosis is a regulated form of necrotic cell death caused by an iron-dependent accumulation of oxidized phospholipids in cellular membranes, which culminates in plasma membrane rupture (PMR) and cell lysis. PMR is also a hallmark of other types of programmed necrosis, such as pyroptosis and necroptosis, where it is initiated by dedicated pore-forming cell death executors. Yet, whether ferroptosis-associated PMR is actively executed by a protein or driven by osmotic pressure remains unknown. Here, we investigated the role of ninjurin-1 (NINJ1), the recently identified executor of pyroptosis-associated PMR, in ferroptosis. We report that during ferroptosis NINJ1 oligomerizes and that Ninj1-deficiency protects macrophages and fibroblasts from ferroptosis-associated PMR. Mechanistically, we find that NINJ1 is dispensable for the early steps of ferroptosis, such as lipid peroxidation, channel-mediated calcium influx and cell swelling. By contrast, NINJ1 is required for early loss of plasma membrane integrity, an event that precedes complete PMR. Furthermore, NINJ1 mediates the release of cytosolic proteins and danger-associated molecular patterns (DAMPs) from ferroptotic cells, suggesting that targeting NINJ1 could be a therapeutic option to reduce ferroptosis-associated inflammation.
2024-02-15 | PXD047622 | Pride
Project description:In our investigation of age-related changes in brown adipose tissue, we have identified two distinct populations of brown adipocytes characterized by high and low expression of uncoupling protein 1 (UCP1). We observed that with aging, the proportion of UCP1-low adipocytes increases, and these cells notably express genes associated with pyroptosis, an inflammatory form of programmed cell death.
2024-02-24 | GSE248814 | GEO
Project description:The deficiency of LKB1 in tumor cells impairs their ability to sense metabolic stress appropriately,ultimately leading to redox imbalance. LKB1-deficient NSCLC cells predominantly take up ascorbic acid. Inflammatory PCD, including necroptosis, pyroptosis and PANoptosis, could release inflammatory mediators and switch the inflammatory state of TIME. Previous study demonstrated that high-dose AA could promote lung cancer cell death, but the modality of cell death still remained unclear. To further investigated the precise modality of the above inflammatory PCD, we performed RNA sequencing on cells with deficient or intact LKB1 pretreated with high-dose AA or not and then analyzed the established different forms of programmed cell death signaling gene.
2025-06-28 | GSE269742 | GEO
Project description:Corneal wound healing involves complex cellular processes, including keratocyte cell death, which plays a pivotal role in initiating tissue repair. Recent studies suggest that pyroptosis, characterized by the release of pro-inflammatory factors, occurs during tissue repair which may also contribute to the inflammatory phase of corneal wound healing. In this study, we investigated the nature of cell death in human keratocytes treated with nigericin, a known pyroptosis inducer. Surprisingly, nigericin triggered a unique form of non-inflammatory cell death marked by extensive vacuolation, resembling paraptosis. Proteomic analysis revealed that our human keratocytes lack key components of the canonical pyroptosis pathway, including NLRP3, ASC, and caspase-1, potentially explaining the absence of pyroptosis in these cells. This process was further confirmed by the absence of caspase-3 activation and lack of ER stress, alongside increased autophagic marker LC3-II accumulation. These findings suggest that nigericin triggers a paraptosis-like cell death in keratocytes, rather than pyroptosis, highlighting an alternative mechanism of cell death in corneal wound healing that warrants further exploration.
2025-06-30 | PXD058468 | Pride
Project description:Pyroptosis is a recently discovered form of lytic cell death that is characterized by cell swelling and formation of pores and large bubbles on the plasma membrane. We find radiation could induce pyroptosis in human colorectal cancer HCT116 cells, and irradiation induces pyroptosis in mouse normal intestine MODEK cells only after 36 hours and over 8.0 Gy. In view of the significant pyroptosis effect of MODE-K cells, we selected 4Gy and 12Gy, 24h and 48h for experiments. After ONT full-length transcriptome sequencing, the cell pyroptosis model can screen out the differential genes related to cell pyroptosis, which is helpful to further explore the mechanism of pyroptosis of MODE-K cells.
2024-08-01 | GSE211709 | GEO
Project description:Post-traumatic neuroinflammation is a key driver of secondary injury after traumatic brain injury (TBI). Pyroptosis, a proinflammatory form of programmed cell death, considerably activates strong neuroinflammation and amplifies the inflammatory response by releasing inflammatory contents. Therefore, treatments targeting pyroptosis may beneficially effects for the treatment of secondary brain damage after TBI. Herein, a cysteine-alanine-glutamine-lysine (CAQK) peptide-modified β-lactoglobulin (β-LG) nanoparticle was constructed to deliver disulfiram (DSF), C-β-LG/DSF, to inhibit pyroptosis and decrease neuroinflammation, thereby preventing TBI-induced secondary injury. In the post-TBI mice model, C-β-LG/DSF selectively targets the injured brain, increases DSF accumulation, and extends the time of the systemic circulation of DSF. C-β-LG/DSF can alleviate brain edema and inflammatory response, inhibit secondary brain injury, promote learning, and improve memory recovery in mice after trauma. Therefore, this study likely provided a new approach for reducing the secondary spread of TBI.
2024-01-17 | GSE244966 | GEO
Project description:Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared to tissue-specific progenitors. Direct interrogation of iron uptake demonstrated CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin - two core iron regulators - to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, and on which CSCs have an epigenetically programmed, targetable dependence.
2015-09-30 | GSE72203 | GEO