NINJ1 in Cell Death and Ferroptosis: Implications for Tumor Invasion and Metastasis DOI Open Access
Ssu-Yu Chen,

Ing-Luen Shyu,

Jen‐Tsan Chi

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 800 - 800

Published: Feb. 26, 2025

NINJ1 was initially recognized for its role in nerve regeneration and cellular adhesion. Subsequent studies have uncovered participation cancer progression, where regulates critical steps tumor metastasis, such as cell migration invasion. More recently, has emerged a multifunctional protein mediating plasma membrane rupture (PMR) several lytic death processes, including apoptosis, necroptosis, pyroptosis. However, ferroptosis-an iron-dependent form of characterized by lipid peroxidation-remained unclear until 2024. Ferroptosis is suppression mechanism that may be particularly relevant to detached metastatic cells. This review explores the invasion focusing on regulation ferroptosis via non-canonical distinct from other deaths. We discuss process implications metastasis. Furthermore, we recent highlighting diverse roles regulation, canonical function PMR modulating intracellular levels glutathione (GSH) coenzyme A (CoA) interaction with xCT anti-porter. Given been associated suppression, elimination treatment-resistant cells, dormancy, NINJ1's modulation presents promising therapeutic target inhibiting Understanding dual promoting or restraining depending context could open avenues novel anti-cancer strategies enhance ferroptotic vulnerability tumors.

Language: Английский

Cardiovascular disease: Mitochondrial dynamics and mitophagy crosstalk mechanisms with novel programmed cell death and macrophage polarisation DOI Creative Commons
Dandan Liu,

Hewei Qin,

Yang Gao

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107258 - 107258

Published: June 21, 2024

Several cardiovascular illnesses are associated with aberrant activation of cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis and macrophage polarisation as hallmarks contributing to vascular damage abnormal cardiac function. Meanwhile, these three novel forms dysfunction closely related mitochondrial homeostasis. Mitochondria the main organelles that supply energy maintain Mitochondrial stability is maintained through a series regulatory pathways, such fission, fusion mitophagy. Studies have shown (e.g., impaired dynamics mitophagy) promotes ROS production, leading oxidative stress, which induces M1 phenotypic polarisation. Therefore, an in-depth knowledge dynamic regulation mitochondria during necessary understand disease development. This paper systematically summarises impact changes in mitophagy on regulating dysfunctions promote understanding pathogenesis diseases provide corresponding theoretical references for treating diseases.

Language: Английский

Citations

20
The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders DOI Creative Commons

Yejia Xu,

Bowen Jia,

Jing Li

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 395 - 395

Published: March 26, 2024

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain traumatic injury, epilepsy, depression, more. The involved pathogenesis is notably intricate diverse. Ferroptosis neuroinflammation play pivotal roles elucidating the causes of cognitive impairment stemming from these diseases. Given concurrent occurrence ferroptosis due metabolic shifts such as iron ROS, well their critical central nervous disorders, investigation into co-regulatory mechanism has emerged a prominent area research. This paper delves mechanisms along with interrelationship. It specifically emphasizes core molecules within shared pathways governing neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, how different immune cells structures contribute dysfunction through mechanisms. Researchers’ findings suggest that mutually promote each other may represent key factors progression disorders. A deeper comprehension common pathway between cellular holds promise for improving symptoms prognosis related

Language: Английский

Citations

18
In defence of ferroptosis DOI Creative Commons
Francesca M. Alves, Darius J.R. Lane,

Triet Phu Minh Nguyen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 2, 2025

Abstract Rampant phospholipid peroxidation initiated by iron causes ferroptosis unless this is restrained cellular defences. Ferroptosis increasingly implicated in a host of diseases, and unlike other cell death programs the physiological initiation conceived to occur not an endogenous executioner, but withdrawal guardians that otherwise constantly oppose induction. Here, we profile key ferroptotic defence strategies including regulation, modulation enzymes metabolite systems: glutathione reductase (GR), suppressor protein 1 (FSP1), NAD(P)H Quinone Dehydrogenase (NQO1), Dihydrofolate (DHFR), retinal reductases dehydrogenases (RDH) thioredoxin (TR). A common thread uniting all metabolites combat lipid during dependence on reductant, nicotinamide adenine dinucleotide phosphate (NADPH). We will outline how cells control central carbon metabolism produce NADPH necessary precursors defend against ferroptosis. Subsequently discuss evidence for dysregulation different disease contexts glucose-6-phosphate dehydrogenase deficiency, cancer neurodegeneration. Finally, several anti-ferroptosis therapeutic spanning use radical trapping agents, dependent redox support highlight current landscape clinical trials focusing

Language: Английский

Citations

2
Tailoring traditional Chinese medicine in cancer therapy DOI Creative Commons

Shuiquan Li,

Xi Chen, Hui Shi

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 21, 2025

Language: Английский

Citations

2
METTL16-SENP3-LTF axis confers ferroptosis resistance and facilitates tumorigenesis in hepatocellular carcinoma DOI Creative Commons
Jialin Wang,

Mengxi Xiu,

Jin Wang

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Sept. 2, 2024

Ferroptosis, characterized by iron-dependent lipid peroxidation, emerges as a promising avenue for hepatocellular carcinoma (HCC) intervention due to its tumor susceptibility. RNA N6-methyladenosine (m6A) modification has been involved in several types of regulated cell death. However, the roles and molecular mechanisms m6A-related regulators HCC ferroptosis remain unclear. By examining series m6A enzymes upon induction or inhibition, we identified METTL16 novel ferroptotic repressor cells. The on development were investigated multiple lines, human organoids, subcutaneous xenografts MYC/Trp53−/− model hepatocyte-specific Mettl16 knockout overexpression mice. underlying mechanism was elucidated with MeRIP/RIP-qPCR, luciferase assay, Co-IP assay Mass Spectrometry. clinical significance relevance evaluated samples. High expression confers resistance cells mouse models, promotes viability progression. Mechanistically, collaborates IGF2BP2 modulate SENP3 mRNA stability an m6A-dependent manner, latter impedes proteasome-mediated ubiquitination degradation Lactotransferrin (LTF) via de-SUMOylation. Elevated LTF facilitates chelation free iron reduces liable pool level. are implicated METTL16-mediated progression anti-ferroptotic effects both vivo vitro. Clinically, positively correlated, high predicts poor prognosis Our study reveals new METTL16-SENP3-LTF signaling axis regulating driving development. Targeting this is strategy sensitizing against HCC.

Language: Английский

Citations

9
Ferroptosis: mechanisms and therapeutic targets DOI Creative Commons
Qian Zhou, Yu Meng,

Jiayuan Le

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(12)

Published: Nov. 20, 2024

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation in membrane phospholipids. Since its identification 2012, extensive research has unveiled involvement the pathophysiology numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious autoimmune conditions, metabolic and skin diseases. Oxidizable lipids, overload iron, compromised antioxidant systems are known as critical prerequisites for driving overwhelming peroxidation, ultimately leading to plasma rupture ferroptotic death. However, precise regulatory networks governing ferroptosis ferroptosis-targeted therapy these diseases remain largely undefined, hindering development pharmacological agonists antagonists. In this review, we first elucidate core mechanisms summarize epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, N6-methyladenosine modification) nonepigenetic genetic mutations, transcriptional regulation, posttranslational modifications). We then discuss association between disease pathogenesis explore therapeutic approaches targeting ferroptosis. also introduce potential clinical monitoring strategies Finally, put forward several unresolved issues which progress needed better understand hope review will offer promise application therapies context human health disease.

Language: Английский

Citations

9
Targeting ferroptosis in ovarian cancer: Novel strategies to overcome chemotherapy resistance DOI Creative Commons
Celine Kapper, Peter Oppelt, Barbara Arbeithuber

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 349, P. 122720 - 122720

Published: May 16, 2024

This review investigates the role of ferroptosis in combating chemotherapy resistance ovarian cancer, with a focus on its underlying mechanisms and therapeutic implications.

Language: Английский

Citations

8
Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance DOI Creative Commons
Peng Zhao,

Shuangshuang Yin,

Yuling Qiu

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature

Language: Английский

Citations

1
DNA Damage-Induced Ferroptosis: A Boolean Model Regulating p53 and Non-Coding RNAs in Drug Resistance DOI Creative Commons
Shantanu Gupta, Daner A. Silveira, José C. M. Mombach

et al.

Proteomes, Journal Year: 2025, Volume and Issue: 13(1), P. 6 - 6

Published: Jan. 20, 2025

The tumor suppressor p53, in its wild-type form, plays a central role cellular homeostasis by regulating senescence, apoptosis, and autophagy within the DNA damage response (DDR). Recent findings suggest that p53 also governs ferroptosis, an iron-dependent cell death process driven lipid peroxidation. Post-translational modifications of generate proteoforms significantly enhance functional diversity these mechanisms. A key target this is cystine/glutamate transporter (xCT), which essential for redox balance ferroptosis resistance. Additionally, p53-induced miR-34c-5p suppresses cancer proliferation drug resistance modulating Myc, oncogene further influenced non-coding RNAs like circular RNA NOTCH1 (CricNOTCH1) long MALAT1. However, exact molecules remains unclear. To address this, we introduce first dynamic Boolean model delineates influence ncRNAs on senescence DDR context. Validated through gain- loss-of-function perturbations, our closely aligns with experimental observations cancers such as oral squamous carcinoma, nasopharyngeal osteosarcoma. identifies crucial positive feedback loops (CricNOTCH1/miR-34c/Myc, MALAT1/miR-34c/Myc, Myc/xCT) highlights therapeutic potential using to combat induce death.

Language: Английский

Citations

1
Relevance of proteomics and metabolomics approaches to overview the tumorigenesis and better management of cancer DOI
Pooja Singh, Yashika Walia, Shagun Gupta

et al.

3 Biotech, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 11, 2025

Language: Английский

Citations

1