Modulation of YBX1-mediated PANoptosis inhibition by PPM1B and USP10 confers chemoresistance to oxaliplatin in gastric cancer DOI Creative Commons
Chunlin Lin, Penghang Lin,

Hengxin Yao

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 587, P. 216712 - 216712

Published: Feb. 15, 2024

Gastric cancer (GC) is a common malignant tumor of the digestive tract, and chemoresistance significantly impacts GC patients' prognosis. PANoptosis has been associated with oxaliplatin-induced cell death. However, direct regulatory role YBX1 in cellular through remains unclear. In this study, we investigated impact on regulating its influence resistance gastric cells to oxaliplatin. Through overexpression silencing experiments, assessed YBX1's effect proliferation regulation cells. Additionally, identified PPM1B USP10 as interacting proteins confirmed their molecular function protein expression levels. Our results demonstrate that suppresses PANoptosis, leading enhanced Furthermore, found play critical roles YBX1-mediated inhibition. directly interacts YBX1, causing dephosphorylation at serine 314 residue. This process affects deubiquitination mediated by USP10, resulting decreased levels impacting oxaliplatin discovered 314th amino acid profound own abundance, thereby affecting functionality YBX1. conclusion, our study reveals significance PPM1B-mediated USP10-mediated sensitivity These findings offer potential therapeutic strategy for patients oxaliplatin-resistant cancer.

Language: Английский

Sulconazole Induces PANoptosis by Triggering Oxidative Stress and Inhibiting Glycolysis to Increase Radiosensitivity in Esophageal Cancer DOI Creative Commons

Lu-Xin Liu,

Jing-Hua Heng,

Dan-Xia Deng

et al.

Molecular & Cellular Proteomics, Journal Year: 2023, Volume and Issue: 22(6), P. 100551 - 100551

Published: April 18, 2023

Esophageal cancer is the seventh most common in world. Although traditional treatment methods such as radiotherapy and chemotherapy have good effects, their side effects drug resistance remain problematic. The repositioning of function provides new ideas for research development anticancer drugs. We previously showed that Food Drug Administration-approved sulconazole can effectively inhibit growth esophageal cells, but its molecular mechanism not clear. Here, our study demonstrated had a broad spectrum effects. It only proliferation also migration cells. Both transcriptomic sequencing proteomic could promote various types programmed cell death glycolysis related pathways. Experimentally, we found induced apoptosis, pyroptosis, necroptosis, ferroptosis. Mechanistically, triggered mitochondrial oxidative stress inhibited glycolysis. Finally, low-dose increase radiosensitivity Taken together, these findings provide strong laboratory evidence clinical application cancer.

Language: Английский

Citations

47
PANoptosis: bridging apoptosis, pyroptosis, and necroptosis in cancer progression and treatment DOI Creative Commons
Jie Gao,

Anying Xiong,

Jiliu Liu

et al.

Cancer Gene Therapy, Journal Year: 2024, Volume and Issue: 31(7), P. 970 - 983

Published: March 29, 2024

Abstract This comprehensive review explores the intricate mechanisms of PANoptosis and its implications in cancer. PANoptosis, a convergence apoptosis, pyroptosis, necroptosis, plays crucial role cell death immune response regulation. The study delves into molecular pathways each mechanism their crosstalk within emphasizing shared components like caspases PANoptosome complex. It highlights significant various cancers, including respiratory, digestive, genitourinary, gliomas, breast showing impact on tumorigenesis patient survival rates. We further discuss interwoven relationship between tumor microenvironment (TME), illustrating how influences behavior progression. underscores dynamic interplay tumors microenvironments, focusing roles different cells interactions with cancer cells. Moreover, presents new breakthroughs therapy, potential targeting to enhance anti-tumor immunity. outlines strategies manipulate for therapeutic purposes, such as key signaling molecules caspases, NLRP3, RIPK1, RIPK3. novel treatments immunogenic PANoptosis-initiated therapies nanoparticle-based is also explored.

Language: Английский

Citations

36
A slow-releasing donor of hydrogen sulfide inhibits neuronal cell death via anti-PANoptosis in rats with spinal cord ischemia‒reperfusion injury DOI Creative Commons
Lei Xie, Hang Wu,

Qiuping He

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 12, 2024

Abstract Background Spinal cord ischemia‒reperfusion injury (SCIRI) can lead to paraplegia, which leads permanent motor function loss. It is a disastrous complication of surgery and causes tremendous socioeconomic burden. However, effective treatments for SCIRI are still lacking. PANoptosis consists three kinds programmed cell death, pyroptosis, apoptosis, necroptosis, may contribute ischemia‒reperfusion-induced neuron death. Previous studies have demonstrated that hydrogen sulfide (H 2 S) exerts neuroprotective effect in many neurodegenerative diseases. whether H S anti-PANoptosis the progression acute remains unclear. Thus, this study we aimed explore role its underlying mechanisms. Methods Measurements lower limb function, neuronal activity, microglia/macrophage histopathological examinations, biochemical levels were performed examine efficacy further demonstrate mechanism treatment SCIRI. Results The results showed GYY4137 (a slow-releasing donor) attenuated loss Nissl bodies after improved BBB score. Additionally, number TUNEL-positive cleaved caspase-3-positive cells was decreased, upregulation expression caspase-8, caspase-3, Bax, Bad downregulation Bcl-2 reversed administration. Meanwhile, both activation p-MLKL, p-RIP1, p-RIP3, along with PI-positive RIP3-positive neurons, decreased GYY4137-treated rats. Furthermore, administration reduced NLRP3, caspase-1 GSDMD, colocalization NeuN/NLRP3 Iba1/interleukin-1β-expressing cells, inhibited proinflammatory factors polarization. Conclusions ameliorated spinal loss, prevented dysfunction SCIRI, exerted via inhibition overactivated microglia-mediated neuroinflammation

Language: Английский

Citations

21
PANoptosis subtypes predict prognosis and immune efficacy in gastric cancer DOI
Zitao Liu, Liang Sun, Xingyu Peng

et al.

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(5-6), P. 799 - 815

Published: Feb. 12, 2024

Language: Английский

Citations

17
Sensing of mitochondrial DNA by ZBP1 promotes RIPK3-mediated necroptosis and ferroptosis in response to diquat poisoning DOI

Kunmei Lai,

Junjie Wang,

Siyi Lin

et al.

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: 31(5), P. 635 - 650

Published: March 16, 2024

Language: Английский

Citations

17
Integrative analysis of immunogenic PANoptosis and experimental validation of cinobufagin-induced activation to enhance glioma immunotherapy DOI Creative Commons

Yonghua Cai,

Heng Xiao, Shuaishuai Xue

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 3, 2025

Glioma, particularly glioblastoma (GBM), is a highly aggressive tumor with limited responsiveness to immunotherapy. PANoptosis, form of programmed cell death merging pyroptosis, apoptosis, and necroptosis, plays an important role in reshaping the microenvironment (TME) enhancing immunotherapy effectiveness. This study investigates PANoptosis dynamics glioma explores therapeutic potential its activation, through natural compounds such as cinobufagin. We comprehensively analyzed PANoptosis-related genes (PANoRGs) multiple cohorts, identifying different patterns constructing enrichment score (PANoScore) evaluate relationship patient prognosis immune activity. Cinobufagin, identified activator, was evaluated for ability induce enhance anti-tumor responses both vitro vivo GBM models. Our findings indicate that high PANoScore gliomas showed increased infiltration, effector T cells, enhanced sensitivity immunotherapies. Cinobufagin effectively induced leading immunogenic death, facilitated tumor-associated microglia/macrophages (TAMs) polarization towards M1-like phenotype while augmenting CD4+/CD8 + infiltration activation. Importantly, cinobufagin combined anti-PD-1 therapy exhibited significant synergistic effects prolonged survival These highlight PANoptosis-targeting agents, cinobufagin, combination immunotherapy, offering promising approach convert "cold" tumors into "hot" ones improving treatment outcomes.

Language: Английский

Citations

2
Histone lactylation drives liver cancer metastasis by facilitating NSF1-mediated ferroptosis resistance after microwave ablation DOI Creative Commons
Jiayan Huang, Huijing Xie,

Ju Li

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103553 - 103553

Published: Feb. 15, 2025

Language: Английский

Citations

2
Regulated cell death in cancer: from pathogenesis to treatment DOI Creative Commons
Linjing Gong, Dong Huang,

Yujun Shi

et al.

Chinese Medical Journal, Journal Year: 2022, Volume and Issue: 136(6), P. 653 - 665

Published: Aug. 10, 2022

Abstract Regulated cell death (RCD), including apoptosis, pyroptosis, necroptosis, and ferroptosis, is regulated by a series of evolutionarily conserved pathways, required for development tissue homeostasis. Based on previous genetic biochemical explorations subroutines, the characteristics each are generally considered distinctive. However, recent in-depth studies noted presence crosstalk between different forms RCD; hence, concept PANoptosis appeared. Cancer, complex disease, characterized stepwise deregulation apoptosis proliferation, with significant morbidity mortality globally. At present, RCD as well intricate relationships mainly focus infectious diseases, their roles in cancer remain unclear. As cancers dysregulated inflammatory responses, most current treatment strategies aim to selectively induce via pathways cells. In this review, we describe five types detail respect tumorigenesis progression. The potential value some these key effector molecules tumor diagnosis therapeutic response has also been raised. We then review highlight progress based ferroptosis induced small-molecule compounds, immune checkpoint inhibitors, nanoparticles. Together, findings may provide meaningful evidence fill gaps pathogenesis develop better strategies.

Language: Английский

Citations

56
Single cell analysis of PANoptosome cell death complexes through an expansion microscopy method DOI
Yaqiu Wang, Pandian Nagakannan, Joo‐Hui Han

et al.

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(10)

Published: Sept. 28, 2022

Language: Английский

Citations

46
Current evidence and therapeutic implication of PANoptosis in cancer DOI Creative Commons
Dickson Kofi Wiredu Ocansey, Fei Qian,

Peipei Cai

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 14(2), P. 640 - 661

Published: Dec. 26, 2023

Regulated cell death (RCD) is considered a critical pathway in cancer therapy, contributing to eliminating cells and influencing treatment outcomes. The application of RCD marked by its potential targeted therapy immunotherapy. As type RCD, PANoptosis has emerged as unique form programmed (PCD) characterized features pyroptosis, apoptosis, necroptosis but cannot be fully explained any these pathways alone. It regulated multi-protein complex called the PANoptosome. relatively new concept first described 2019, been shown play role many diseases, including cancer, infection, inflammation. This study reviews PCD particularly emergence implication developing therapeutic strategies for cancer. Studies have that characterization patterns can predict survival response immunotherapy chemotherapy, highlighting used target treatment. also plays limiting spread cells. allows elimination multiple address various challenges treatment, drug resistance immune evasion. Moreover, active investigation mechanisms agents induce likely yield effective treatments improve patient Research on still ongoing, it rapidly evolving field with lead

Language: Английский

Citations

37