Unveiling ferroptosis: a new frontier in skin disease research DOI Creative Commons
Ke Wang,

Yumeng Lin,

Dan Zhou

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 4, 2024

Ferroptosis, a form of regulated cell death distinct from apoptosis, necrosis, and autophagy, is increasingly recognized for its role in skin disease pathology. Characterized by iron accumulation lipid peroxidation, ferroptosis has been implicated the progression various conditions, including psoriasis, photosensitive dermatitis, melanoma. This review provides an in-depth analysis molecular mechanisms underlying compares cellular effects with other forms context health disease. We systematically examine five specific diseases, ichthyosis, polymorphous light eruption (PMLE), vitiligo, melanoma, detailing influence on pathogenesis progression. Moreover, we explore current clinical landscape ferroptosis-targeted therapies, discussing their potential managing treating diseases. Our aim to shed therapeutic modulating research practice.

Language: Английский

CYP51A1 drives resistance to pH-dependent cell death in pancreatic cancer DOI Creative Commons
Fangquan Chen, Hu Tang, Changfeng Li

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 7, 2025

Disrupted pH homeostasis can precipitate cell death and represents a viable therapeutic target in oncological interventions. Here, we utilize mass spectrometry-based drug analysis, transcriptomic screens, lipid metabolomics to explore the metabolic mechanisms underlying pH-dependent death. We reveal CYP51A1, gene involved cholesterol synthesis, as key suppressor of alkalization-induced pancreatic cancer cells. Inducing intracellular alkalization by small molecule JTC801 leads decrease endoplasmic reticulum levels, subsequently activating SREBF2, transcription factor responsible for controlling expression genes biosynthesis. Specifically, SREBF2-driven upregulation CYP51A1 prevents accumulation within lysosomes, leading TMEM175-dependent lysosomal proton efflux, ultimately resulting inhibition In animal models, including xenografts, syngeneic orthotopic, patient-derived genetic or pharmacological enhances effectiveness suppressing tumors. These findings demonstrate role CYP51A1-dependent pathway inhibiting highlight its potential targetable vulnerability cancer. Previously, opioid analgesic JCT801 was reported induce via disruption authors investigate JCT801-induced death, identifying synthesis gene,

Language: Английский

Citations

1
Ferroptosis: a novel mechanism of cell death in ophthalmic conditions DOI Creative Commons
Yaqi Yang,

Yumeng Lin,

Zhongyu Han

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 27, 2024

Ferroptosis, a new type of programmed cell death proposed in recent years, is characterized mainly by reactive oxygen species and iron-mediated lipid peroxidation differs from death, such as apoptosis, necrosis, autophagy. Ferroptosis associated with variety physiological pathophysiological processes. Recent studies have shown that ferroptosis can aggravate or reduce the occurrence development diseases targeting metabolic pathways signaling tumors, ischemic organ damage, other degenerative related to peroxidation. Increasing evidence suggests closely linked onset progression various ophthalmic conditions, including corneal injury, glaucoma, age-related macular degeneration, diabetic retinopathy, retinal detachment, retinoblastoma. Our review current research on reveals significant advancements our understanding pathogenesis, aetiology, treatment these conditions.

Language: Английский

Citations

5
Macropinocytosis inhibits alkaliptosis in pancreatic cancer cells through fatty acid uptake DOI
Fangquan Chen, Hu Tang, Junhao Lin

et al.

Carcinogenesis, Journal Year: 2024, Volume and Issue: unknown

Published: July 14, 2024

Alkaliptosis, a form of regulated cell death, is characterized by lysosomal dysfunction and intracellular pH alkalinization. The pharmacological induction alkaliptosis using the small molecule compound JTC801 has emerged as promising anticancer strategy in various types cancers, particularly pancreatic ductal adenocarcinoma (PDAC). In this study, we investigate novel mechanism which macropinocytosis, an endocytic process involving uptake extracellular material, promotes resistance to human PDAC cells. Through lipid metabolomics analysis functional studies, demonstrate that inhibition fatty acids, such oleic acid, not dependent on endogenous synthetic pathways but rather exogenous facilitated macropinocytosis. Consequently, targeting macropinocytosis through approaches (e.g., EIPA or EHoP-016) genetic interventions RAC1 knockdown) effectively enhances JTC801-induced These findings provide compelling evidence modulation can increase sensitivity cancer cells inducers.

Language: Английский

Citations

4
ZACN Associated with Poor Prognosis Promotes Proliferation of Kidney Renal Clear Cell Carcinoma Cells by Inhibiting JTC801-Induced Alkaliptosis DOI
Yifan Li, Can Li

Applied Biochemistry and Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

Citations

0
Cetylpyridinium chloride triggers paraptosis to suppress pancreatic tumor growth via the ERN1-MAP3K5-p38 pathway DOI Creative Commons

Hu Tang,

Fangquan Chen,

Wanli Gao

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(8), P. 110598 - 110598

Published: July 26, 2024

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive solid malignancy with low 5-year survival and limited treatment options. We conducted an unbiased screening using FDA-approved drug demonstrated that cetylpyridinium chloride (CPC), component commonly found in mouthwash known for its robust bactericidal antifungal attributes, exhibits anticancer activity against human PDAC cells. CPC inhibited cell growth proliferation by inducing paraptosis, rather than apoptosis. Mechanistically, induced paraptosis through the initiation of endoplasmic reticulum stress, leading to accumulation misfolded proteins. Subsequently, stress nucleus signaling 1 (ERN1)-mitogen-activated protein kinase 5 (MAP3K5)-p38 mitogen-activated (MAPK) pathway was activated, ultimately culminating induction paraptosis.

Language: Английский

Citations

1
ITCH inhibits alkaliptosis in human pancreatic cancer cells through YAP1-dependent SLC16A1 activation DOI

Xiutao Cai,

Fangquan Chen, Hu Tang

et al.

The International Journal of Biochemistry & Cell Biology, Journal Year: 2024, Volume and Issue: 175, P. 106646 - 106646

Published: Aug. 23, 2024

Language: Английский

Citations

1
Molecular characteristics and immune microenvironment of gastrointestinal stromal tumours: targets for therapeutic strategies DOI Creative Commons
Yu Yang,

Mengdie Yu,

Lijie Luo

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: July 12, 2024

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours, arising mainly from interstitial cells of Cajal (ICCs) gastrointestinal tract. As radiotherapy and chemotherapy generally ineffective for GISTs, current primary treatment is surgical resection. However, resection not choice patients. Therefore, new therapeutic strategies urgently needed. Targeted therapy, represented by tyrosine kinase inhibitors (TKIs), immunotherapy, immune checkpoint inhibitor therapies chimeric antigen receptor T-cell immunotherapy (CAR-T), offer options in GISTs have shown promising responses. In this review, we summarize molecular classification microenvironment discuss corresponding targeted therapy options. This updated knowledge may provide more future applications GISTs.

Language: Английский

Citations

0
Unveiling ferroptosis: a new frontier in skin disease research DOI Creative Commons
Ke Wang,

Yumeng Lin,

Dan Zhou

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 4, 2024

Ferroptosis, a form of regulated cell death distinct from apoptosis, necrosis, and autophagy, is increasingly recognized for its role in skin disease pathology. Characterized by iron accumulation lipid peroxidation, ferroptosis has been implicated the progression various conditions, including psoriasis, photosensitive dermatitis, melanoma. This review provides an in-depth analysis molecular mechanisms underlying compares cellular effects with other forms context health disease. We systematically examine five specific diseases, ichthyosis, polymorphous light eruption (PMLE), vitiligo, melanoma, detailing influence on pathogenesis progression. Moreover, we explore current clinical landscape ferroptosis-targeted therapies, discussing their potential managing treating diseases. Our aim to shed therapeutic modulating research practice.

Language: Английский

Citations

0