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

и другие.

Cell Death Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Апрель 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

Язык: Английский

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

Longteng Liang,

Siyi Liu

и другие.

Trends in Molecular Medicine, Год журнала: 2023, Номер 29(9), С. 753 - 764

Опубликована: Июнь 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

Язык: Английский

Процитировано

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

Meisi Yan,

Tong Liu

и другие.

Nature Cell Biology, Год журнала: 2023, Номер 25(5), С. 714 - 725

Опубликована: Май 1, 2023

Язык: Английский

Процитировано

102
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

и другие.

Cell Reports, Год журнала: 2023, Номер 42(8), С. 112945 - 112945

Опубликована: Авг. 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.

Язык: Английский

Процитировано

86
Role of ferroptosis on tumor progression and immunotherapy DOI Creative Commons

Deting Gong,

Mingjun Chen, Yuhan Wang

и другие.

Cell Death Discovery, Год журнала: 2022, Номер 8(1)

Опубликована: Окт. 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.

Язык: Английский

Процитировано

85
Elevated FSP1 protects KRAS-mutated cells from ferroptosis during tumor initiation DOI Creative Commons
Fabienne Müller, Jonathan K.M. Lim, Christina M. Bebber

и другие.

Cell Death and Differentiation, Год журнала: 2022, Номер 30(2), С. 442 - 456

Опубликована: Ноя. 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

Язык: Английский

Процитировано

85
Ferroptosis in health and disease DOI Creative Commons
Carsten Berndt, Hamed Alborzinia,

Vera Skafar Amen

и другие.

Redox Biology, Год журнала: 2024, Номер 75, С. 103211 - 103211

Опубликована: Май 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

Язык: Английский

Процитировано

79
Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer DOI Creative Commons

Taegeun Bae,

Steffanus Pranoto Hallis, Mi‐Kyoung Kwak

и другие.

Experimental & Molecular Medicine, Год журнала: 2024, Номер 56(3), С. 501 - 514

Опубликована: Март 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.

Язык: Английский

Процитировано

70
The mechanism of ferroptosis and its related diseases DOI Creative Commons
Shijian Feng, Dan Tang, Yichang Wang

и другие.

Molecular Biomedicine, Год журнала: 2023, Номер 4(1)

Опубликована: Окт. 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.

Язык: Английский

Процитировано

69
Coenzyme Q biochemistry and biosynthesis DOI Creative Commons
Rachel M. Guerra, David J. Pagliarini

Trends in Biochemical Sciences, Год журнала: 2023, Номер 48(5), С. 463 - 476

Опубликована: Янв. 24, 2023

Язык: Английский

Процитировано

63
Ferroptosis: principles and significance in health and disease DOI Creative Commons
Fangquan Chen, Rui Kang, Daolin Tang

и другие.

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Июнь 6, 2024

Abstract Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic pathway in 2012, ferroptosis has emerged crucial mechanism numerous physiological pathological contexts, leading to significant therapeutic advancements across wide range diseases. This review summarizes the fundamental mechanisms regulatory pathways underlying ferroptosis, including both GPX4-dependent -independent antioxidant mechanisms. Additionally, we examine involvement various conditions, cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, metabolic disorders. Specifically, explore role response chemotherapy, radiotherapy, immunotherapy, nanotherapy, targeted therapy. Furthermore, discuss pharmacological strategies for modulating potential biomarkers monitoring this process. Lastly, elucidate interplay between other forms regulated death. Such insights hold promise advancing our understanding context human health disease.

Язык: Английский

Процитировано

58