Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy DOI Creative Commons
Nan Xing,

Qinyun Du,

Sa Guo

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: April 1, 2023

Lung cancer is a common malignant tumor that occurs in the human body and poses serious threat to health quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, radiotherapy. However, due strong metastatic characteristics lung emergence related drug resistance radiation resistance, overall survival rate patients not ideal. There an urgent need develop new strategies or effective drugs treat cancer. Ferroptosis, novel type programmed cell death, different from traditional death pathways such as apoptosis, necrosis, pyroptosis so on. It caused by increase iron-dependent reactive oxygen species intracellular iron overload, which leads accumulation lipid peroxides, thus inducing membrane oxidative damage, affecting normal life process cells, finally promoting ferroptosis. regulation ferroptosis closely physiological it involves metabolism, balance between oxygen-free radical reaction peroxidation. A large number studies have confirmed result combined action cellular oxidation/antioxidant system damage/repair, has great potential application therapy. Therefore, this review aims explore therapeutic targets for clarifying regulatory pathway Based on study ferroptosis, mechanism was understood chemical natural compounds targeting were summarized, with aim providing ideas In addition, also provides basis discovery clinical effectively

Language: Английский

FSP1: a key regulator of ferroptosis DOI Creative Commons
Wentao Li,

Longteng Liang,

Siyi Liu

et al.

Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(9), P. 753 - 764

Published: June 24, 2023

Ferroptosis suppressor protein 1 (FSP1) is one of the main regulatory molecules ferroptosis. FSP1 functions through FSP1-coenzyme Q10 (CoQ10)-NAD(P)H axis and vitamin K redox cycle. regulated by upstream factors, including transcription factors noncoding RNA (ncRNA), subject to epigenetic modifications, which affect progress FSP1-related diseases. closely associated with poor prognosis malignant tumors plays an important role in disease treatment. This review aims provide a comprehensive understanding ferroptosis regulation summarizing pathways, possible mechanisms involving FSP1, relationship between

Language: Английский

Citations

110
Creatine kinase B suppresses ferroptosis by phosphorylating GPX4 through a moonlighting function DOI
Ke Wu,

Meisi Yan,

Tong Liu

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(5), P. 714 - 725

Published: May 1, 2023

Language: Английский

Citations

98
Role of ferroptosis on tumor progression and immunotherapy DOI Creative Commons

Deting Gong,

Mingjun Chen, Yuhan Wang

et al.

Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: Oct. 26, 2022

Abstract Ferroptosis is triggered by intracellular iron leading to accumulation of lipid peroxidation consequent promotion cell death. Cancer exhibits ability evade ferroptosis activation antioxidant signaling pathways such as SLC7A11/GPX4 axis. In addition transcriptional regulation on NRF2, SREBP1, YAP, and p53, modulated ubiquitination or autophagic degradation. Moreover, zinc Ca 2+ could modulate inducing ferroptosis. Induction enhances immune activity T cells macrophages, which associated with the release DAMPs (damage-associated molecular patterns) IFNγ. Therefore, combined checkpoint inhibitors inducers effectively enhance antitumor immunotherapy, whereas induction impair survival, suggesting that rational therapy for cancer essential. this review, we discussed regulatory role tumor progression immunotherapy.

Language: Английский

Citations

83
HIF-1α drives resistance to ferroptosis in solid tumors by promoting lactate production and activating SLC1A1 DOI Creative Commons
Zhou Yang, Wei Su, Xiyi Wei

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(8), P. 112945 - 112945

Published: Aug. 1, 2023

Solid tumors have developed robust ferroptosis resistance. The mechanism underlying resistance regulation in solid tumors, however, remains elusive. Here, we report that the hypoxic tumor microenvironment potently promotes a hypoxia-inducible factor 1α (HIF-1α)-dependent manner. In combination with HIF-2α, which under hypoxia, HIF-1α is main driver of hypoxia-induced Mechanistically, HIF-1α-induced lactate contributes to pH-dependent manner parallel classical SLC7A11 and FSP1 systems. addition, also enhances transcription SLC1A1, an important glutamate transporter, cystine uptake promote support role hypoxia resistance, silencing sensitizes mouse inducers. conclusion, our results reveal by drives identify alleviation induction as promising therapeutic strategy for tumors.

Language: Английский

Citations

83
Elevated FSP1 protects KRAS-mutated cells from ferroptosis during tumor initiation DOI Creative Commons
Fabienne Müller, Jonathan K.M. Lim, Christina M. Bebber

et al.

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 30(2), P. 442 - 456

Published: Nov. 29, 2022

Oncogenic KRAS is the key driver oncogene for several of most aggressive human cancers. One feature oncogenic expression an early increase in cellular reactive oxygen species (ROS) which promotes transformation if cells manage to escape cell death, mechanisms remain incompletely understood. Here, we identify that as compared WT isogenic systems renders more resistant ferroptosis, a recently described type regulated necrosis. Mechanistically, find with mutant show specific lack ferroptosis-induced lipid peroxidation. Interestingly, KRAS-mutant upregulate ferroptosis suppressor protein 1 (FSP1). Indeed, elevated levels FSP1 are responsible mediating resistance and upregulated consequence MAPK NRF2 pathway activation downstream KRAS. Strikingly, activity soft agar its overexpression sufficient promote spheroid growth 3D cells. Moreover, inhibition accelerates tumor onset absence vivo. Consequently, pharmacological induction pancreatic organoids derived from LsL-KRASG12D expressing mouse model only effective combination inhibition. Lastly, non-small lung cancer (NSCLC), colorectal (CRC) ductal adenocarcinoma (PDAC) respective normal tissue origin correlates PDAC patient datasets. Based on these data, propose must navigate checkpoint by upregulating during establishment. ferroptosis-inducing therapy should be combined inhibitors efficient

Language: Английский

Citations

82
Ferroptosis in health and disease DOI Creative Commons
Carsten Berndt, Hamed Alborzinia,

Vera Skafar Amen

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103211 - 103211

Published: May 30, 2024

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark ferroptosis uncontrolled overwhelming peroxidation polyunsaturated fatty acids contained membrane phospholipids, which eventually leads to rupture the plasma membrane. unique that it essentially spontaneous, uncatalyzed chemical process based on perturbed iron redox homeostasis contributing process, but nonetheless modulated by many metabolic nodes impinge cells' susceptibility ferroptosis. Among affecting sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets treatment numerous currently incurable diseases. Herein, current members Germany-wide research consortium focusing research, well key external experts who made seminal contributions this rapidly growing exciting field gathered provide comprehensive, state-of-the-art review Specific topics include: basic mechanisms, vivo relevance, specialized methodologies, tools, potential contribution disease etiopathology progression. We hope article will not only established scientists newcomers with an overview multiple facets ferroptosis, also encourage additional efforts characterize further molecular pathways modulating ultimate goal develop novel pharmacotherapies tackle associated - or caused

Language: Английский

Citations

69
The mechanism of ferroptosis and its related diseases DOI Creative Commons
Shijian Feng, Dan Tang, Yichang Wang

et al.

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

Citations

64
Coenzyme Q biochemistry and biosynthesis DOI Creative Commons
Rachel M. Guerra, David J. Pagliarini

Trends in Biochemical Sciences, Journal Year: 2023, Volume and Issue: 48(5), P. 463 - 476

Published: Jan. 24, 2023

Language: Английский

Citations

63
Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer DOI Creative Commons

Taegeun Bae,

Steffanus Pranoto Hallis, Mi‐Kyoung Kwak

et al.

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(3), P. 501 - 514

Published: March 1, 2024

Abstract Oxygen is crucial for life and acts as the final electron acceptor in mitochondrial energy production. Cells adapt to varying oxygen levels through intricate response systems. Hypoxia-inducible factors (HIFs), including HIF-1α HIF-2α, orchestrate cellular hypoxic response, activating genes increase supply reduce expenditure. Under conditions of excess resulting oxidative stress, nuclear factor erythroid 2-related 2 (NRF2) activates hundreds oxidant removal adaptive cell survival. Hypoxia stress are core hallmarks solid tumors activated HIFs NRF2 play pivotal roles tumor growth progression. The complex interplay between hypoxia within microenvironment adds another layer intricacy HIF signaling This review aimed elucidate dynamic changes functions pathways emphasizing their implications milieu. Additionally, this explored elaborate NRF2, providing insights into significance these interactions development novel cancer treatment strategies.

Language: Английский

Citations

63
Ferroptosis‐modulating small molecules for targeting drug‐resistant cancer: Challenges and opportunities in manipulating redox signaling DOI Creative Commons
Solveigh C. Koeberle, Anna P. Kipp,

Hermann Stuppner

et al.

Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 43(3), P. 614 - 682

Published: Jan. 19, 2023

Abstract Ferroptosis is an iron‐dependent cell death program that characterized by excessive lipid peroxidation. Triggering ferroptosis has been proposed as a promising strategy to fight cancer and overcome drug resistance in antitumor therapy. Understanding the molecular interactions structural features of ferroptosis‐inducing compounds might therefore open door efficient pharmacological strategies against aggressive, metastatic, therapy‐resistant cancer. We here summarize mechanisms requirements small molecules target central players ferroptosis. Focus placed on (i) glutathione peroxidase (GPX) 4, only GPX isoenzyme detoxifies complex membrane‐bound hydroperoxides, (ii) cystine/glutamate antiporter system X c − for regeneration, (iii) redox‐protective transcription factor nuclear erythroid 2‐related (NRF2), (iv) GPX4 repression combination with induced heme degradation via oxygenase‐1. deduce common ferroptotic activity highlight challenges development. Moreover, we critically discuss potential natural products lead structures provide comprehensive overview structurally diverse biogenic bioinspired trigger iron oxidation, inhibition thioredoxin/thioredoxin reductase or less defined modes action.

Language: Английский

Citations

55