Overcoming cancer chemotherapy resistance by the induction of ferroptosis

Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 66, P. 100916 - 100916

Published: Dec. 29, 2022

Language: Английский

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Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

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Caveolin‐1 promotes cancer progression via inhibiting ferroptosis in head and neck squamous cell carcinoma

Journal of Oral Pathology and Medicine, Journal Year: 2021, Volume and Issue: 51(1), P. 52 - 62

Published: Dec. 7, 2021

Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease worldwide. Much progress has been made in exploring mechanisms improving the therapy of HNSCC, but only a few studies have focused on role ferroptosis HNSCC progression. The current study aimed to reveal underlining that caveolin-1 (CAV1)-ROS (reactive oxygen species)-ferroptosis axis affect process discover novo therapeutic targets or strategies.The CAV1 was analyzed by FerrDb, its clinical significance examined TCGA dataset HNSCC. expressions (CAV1) tissues were measured immunohistochemistry, western blot, real-time PCR assay. Three siRNA sequences designed silence mRNA cells. Cell proliferation, colony formation, wound-healing, transwell assays used examine migration, invasion cancer ROS evaluation intracellular Fe2+ content performed levels ferroptosis.Through analysis with published data, found overexpress than normal tissues, one vital suppressors pathway. Our showed over expressed high level predicted poorer prognosis. Further experiments indicated could inhibit cells promote migration invasion.Overexpression inhibited ferroptosis, leading phenotypes, as well worse regulatory pathway are potential for designing diagnostic combined strategies patients.

Language: Английский

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Ferroptosis-Related Gene Signatures: Prognostic Role in HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 530 - 530

Published: Feb. 5, 2025

Background: Despite advances in the management of head and neck squamous cell carcinoma (HNSCC), prognostic models treatment strategies remain inadequate, particularly for HPV-positive oropharyngeal (OPSCC). The rising incidence OPSCC highlights an urgent need innovative therapeutic approaches. Ferroptosis, a regulated form non-apoptotic death, has gained attention its role cancer progression, but potential as target remains largely unexplored. This study investigates ferroptosis OPSCC, aiming to identify markers provide insights into that could improve patient outcomes. Methods: Thirteen gene expression signatures were retrieved from literature, their performance association immune microenvironment validated on meta-analysis 267 cases (Metanalysis-HPV267) 286 samples BD2Decide project (BD2-HPV286). Results: Our analysis revealed specific ferroptosis-related signatures, FER3, FER4, FER6, FER12, are significantly associated (p-value < 0.05) with high-risk groups adverse tumor features, including suppressed activity enhanced stromal involvement. Elevated CAV1, suppressor, further delineates profiles. Conclusions: These findings highlight significance stratifying patients identifying those poorer clinical Targeting pathways represents novel promising approach addressing unmet effective OPSCC. Future research should focus translating these applications advance precision oncology outcomes this growing population.

Language: Английский

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Role of Ferroptosis in Regulating the Epithelial–Mesenchymal Transition in Pulmonary Fibrosis

Biomedicines, Journal Year: 2023, Volume and Issue: 11(1), P. 163 - 163

Published: Jan. 9, 2023

Idiopathic pulmonary fibrosis is a chronic interstitial lung disease whose pathogenesis involves complex interaction of cell types and signaling pathways. Lung epithelial cells responding to repeated injury experience persistent inflammation sustained epithelial–mesenchymal transition (EMT). The persistence EMT-induced signals generates extracellular matrix accumulation, thereby causing fibrosis. Ferroptosis newly characterized iron-dependent non-apoptotic regulated death. Increased iron accumulation can increase iron-induced oxidant damage in alveolar cells. Studies have demonstrated that steady states oxidation play an important role the death regulation EMT. This review summarizes ferroptosis regulating EMT fibrosis, aiming provide new idea for prevention treatment this disease.

Language: Английский

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Caveolin-1 in endothelial cells: A potential therapeutic target for atherosclerosis

Heliyon, Journal Year: 2023, Volume and Issue: 9(8), P. e18653 - e18653

Published: July 25, 2023

Atherosclerosis (AS) is a chronic vascular disease characterized by lipid accumulation and the activation of inflammatory response; it remains leading nation-wide cause death. Early in progression AS, stimulation pro-inflammatory agonists (TNF-α, LPS, others), oxidized lipoproteins (ox-LDL), biomechanical stimuli (low shear stress) lead to endothelial cell dysfunction. Consequently, crucial investigate how cells respond different stressors ways alter AS development, as they are earliest respond. Caveolin-1 (Cav1) 21-24-kDa membrane protein located caveolae highly expressed cells, which plays vital role regulating transport, responses, various cellular signaling pathways has atherogenic effects. This review summarizes recent studies on structure physiological functions Cav1 outlines potential mechanisms mediates development. Included roles regulation autophagy, response stress, modulation eNOS/NO axis, transduction pathways. provides rationale for proposing novel target prevention well new ideas therapeutic strategies early AS.

Language: Английский

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Caveolin-1 promotes glioma progression and maintains its mitochondrial inhibition resistance

Discover Oncology, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 29, 2023

Glioma is a lethal brain cancer and lacking effective therapies. Challenges include no therapeutic target, intra- intertumoral heterogeneity, inadequate drugs, an immunosuppressive microenvironment, etc. Deciphering the pathogenesis of gliomas finding out working mechanisms are urgent necessary for glioma treatment. Identification prognostic biomarkers targeting biomarker genes will be promising therapy.From our RNA-sequencing data oxidative phosphorylation (OXPHOS)-inhibition sensitive OXPHOS-resistant cell lines, we found that scaffolding protein caveolin 1 (CAV1) highly expressed in resistant group but not group. By comprehensive analysis RNA sequencing data, Whole Genome Bisulfite Sequencing (WGBS) public databases, CAV1 its expression positively related with pathological processes, higher predicts shorter overall survival.Further indicated (1) differentiated CAV1-high groups enriched immune infiltration response; (2) correlated tumor metastasis markers; (3) methylation level promoters lower stage than stage; (4) stemness; (5) renders cells' to inhibitors.Therefore, identified key gene deciphered function progression prognosis, proposing may target gliomas.

Language: Английский

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Exploring beyond Common Cell Death Pathways in Oral Cancer: A Systematic Review

Biology, Journal Year: 2024, Volume and Issue: 13(2), P. 103 - 103

Published: Feb. 6, 2024

Oral squamous cell carcinoma (OSCC) is the most common and lethal type of head neck cancer in world. Variable response acquisition resistance to traditional therapies show that it essential develop novel strategies can provide better outcomes for patient. Understanding cellular molecular mechanisms death control has increased rapidly recent years. Activation pathways, such as emerging forms non-apoptotic programmed death, including ferroptosis, pyroptosis, necroptosis, NETosis, parthanatos, mitoptosis paraptosis, may represent clinically relevant therapeutic opportunities. This systematic review summarizes recently described OSCC, highlighting their potential informing diagnosis, prognosis treatment. Original studies explored any selected deaths OSCC were included. Electronic search, study selection, data collection risk bias assessment tools realized. The literature search was carried out four databases, extracted from 79 articles categorized grouped by death. Ferroptosis, necroptosis represented main studies, with links immunity inflammatory responses, progression OSCC. Harnessing these pathways be useful patient-specific individualized therapy. We perspectives on how different types integrated decision prognosis, treatment

Language: Английский

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Caveolin-1 promotes glioma proliferation and metastasis by enhancing EMT via mediating PAI-1 activation and its correlation with immune infiltrates

Heliyon, Journal Year: 2024, Volume and Issue: 10(2), P. e24464 - e24464

Published: Jan. 1, 2024

Glioma is typically characterized by a poor prognosis and associated with decline in the quality of life as disease advances. However, development effective therapies for glioma has been inadequate. Caveolin-1 (CAV-1) membrane protein that plays role caveolae formation interacts numerous signaling proteins, compartmentalizing them frequently exerting direct control over their activity through binding to its scaffolding domain. Although CAV-1 vital regulator tumour progression, remains unclear. Our findings indicated knockdown significantly inhibits proliferation metastasis glioma. Subsequent mechanistic investigations demonstrated promotes activating photoshatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. Furthermore, we overexpression upregulates expression serpin peptidase inhibitor, class E, member 1 (SERPINE1, also known PAI-1), which serves marker epithelial-mesenchymal transition (EMT) process. Further research showed PAI-1 abolished mediated activation PI3K/Akt In tissues, exhibited correlation unfavorable immune infiltration among patients. summary, our study provided evidence activates pathway upregulating PAI-1, thereby promoting enhanced angiogenesis, involved infiltration.

Language: Английский

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Ferroptosis in head and neck squamous cell carcinoma: from pathogenesis to treatment

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

Published: Jan. 19, 2024

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor worldwide, with high morbidity mortality. Surgery postoperative chemoradiotherapy have largely reduced recurrence fatality rates for HNSCCs. Nonetheless, these therapeutic approaches result in poor prognoses owing to severe adverse reactions development of drug resistance. Ferroptosis a kind programmed death which non-apoptotic. cells can inhibit development. involves various biomolecules signaling pathways, whose expressions be adjusted modulate sensitivity ferroptosis. As tool fight against cancer, activation ferroptosis treatment that has received much attention recent years. Therefore, understanding molecular mechanism HNSCC an essential strategy potential. The important thing treat choose appropriate method. In this review, we discuss defense mechanisms ferroptosis, analyze role inhibition immunity HNSCC, explore inducing including therapy, radiation immunotherapy, nanotherapy comprehensive treatment. We find provides new target

Language: Английский

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