EphA2 as a phase separation protein associated with ferroptosis and immune cell infiltration in colorectal cancer DOI Creative Commons

Yanling Li,

Peng Qiu,

Lujuan Wang

и другие.

Aging, Год журнала: 2023, Номер 15(22), С. 12952 - 12965

Опубликована: Ноя. 16, 2023

Colorectal cancer is one of the most common malignant tumors in digestive system, and its high incidence metastasis rate make it a terrible killer that threatens human health. In-depth exploration targets affecting progression colorectal cells development specific targeted drugs for them are great significance prognosis patients. Erythropoietin-producing hepatocellular A2 (EphA2) member Eph subfamily with tyrosine kinase activity, plays key role regulation signaling pathways related to phenotype various tumor cells, but regulatory mechanism needs be further clarified. Here, we found EphA2 was abnormally highly expressed patients expression had worse prognosis. We also can form liquid-liquid phase separation condensates on cell membrane, which disrupted by ALW-II-41-27, an inhibitor EphA2. In addition, positively correlated ferroptosis-related genes infiltration multiple immune cells. These findings suggest novel membrane protein ability associated ferroptosis infiltration, suggests may inhibited suppressing

Язык: Английский

Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies DOI Creative Commons
Qian Zhou,

Yu Meng,

Daishi Li

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Язык: Английский

Процитировано

177
7-Dehydrocholesterol is an endogenous suppressor of ferroptosis DOI
Florêncio Porto Freitas, Hamed Alborzinia, Ancély Ferreira dos Santos

и другие.

Nature, Год журнала: 2024, Номер 626(7998), С. 401 - 410

Опубликована: Янв. 31, 2024

Язык: Английский

Процитировано

134
Drug-tolerant persister cells in cancer: the cutting edges and future directions DOI
Yi Pu, Lu Li, Haoning Peng

и другие.

Nature Reviews Clinical Oncology, Год журнала: 2023, Номер 20(11), С. 799 - 813

Опубликована: Сен. 25, 2023

Язык: Английский

Процитировано

69
The mechanisms of ferroptosis and its role in atherosclerosis DOI Open Access

Xi Xu,

Xiaodan Xu, Mengqing Ma

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116112 - 116112

Опубликована: Янв. 2, 2024

Ferroptosis is a newly identified form of non-apoptotic programmed cell death, characterized by the iron-dependent accumulation lethal lipid reactive oxygen species (ROS) and peroxidation membrane polyunsaturated fatty acid phospholipids (PUFA-PLs). unique among other death modalities in many aspects. It initiated excessive oxidative damage due to iron overload compromised antioxidant defense systems, including system Xc-/ glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathway GPX4-independent pathways. In past ten years, ferroptosis was reported play critical role pathogenesis various cardiovascular diseases, e.g., atherosclerosis (AS), arrhythmia, heart failure, diabetic cardiomyopathy, myocardial ischemia-reperfusion injury. Studies have dysfunctional metabolism abnormal expression profiles ferroptosis-related factors, iron, GSH, GPX4, ferroportin (FPN), SLC7A11 (xCT), as indicators for atherogenesis. Moreover, plaque cells, i.e., vascular endothelial (VEC), macrophage, smooth muscle (VSMC), positively correlate with atherosclerotic development. Many macromolecules, drugs, Chinese herbs, food extracts can inhibit atherogenic process suppressing cells. contrast, some inducers significant pro-atherogenic effects. However, mechanisms through which affects progression AS still need be well-known. This review summarizes molecular their emerging AS, aimed at providing novel, promising druggable targets anti-AS therapy.

Язык: Английский

Процитировано

43
5-Methylcytosine transferase NSUN2 drives NRF2-mediated ferroptosis resistance in non-small cell lung cancer DOI Creative Commons
Youming Chen,

Zuli Jiang,

Chenxing Zhang

и другие.

Journal of Biological Chemistry, Год журнала: 2024, Номер 300(4), С. 106793 - 106793

Опубликована: Фев. 24, 2024

RNA 5-methylcytosine (m5C) is an abundant chemical modification in mammalian RNAs and plays crucial roles regulating vital physiological pathological processes, especially cancer. However, the dysregulation of m5C its underlying mechanisms non-small cell lung cancer (NSCLC) remain unclear. Here we identified that NSUN2, a key methyltransferase, highly expressed NSCLC tumor tissue. We found elevated NSUN2 expression levels strongly correlate with grade size, predicting poor outcomes for patients. Furthermore, RNA-seq subsequent confirmation studies revealed antioxidant-promoting transcription factor NRF2 target depleting decreases increases sensitivity cells to ferroptosis activators both vitro vivo. Intriguingly, methylated-RIP-qPCR assay results indicated mRNA has higher level when overexpressed but shows no significant changes methyltransferase-deficient group. Mechanistically, confirmed upregulates by enhancing stability through within 5'UTR region recognized specific reader protein YBX1, rather than influencing translation. In rescue experiments, show knocking down diminished proliferation, migration, tolerance mediated overexpression. conclusion, our study unveils novel regulatory mechanism which sustains m5C-YBX1-axis, suggesting targeting regulated pathway might offer promising therapeutic strategies

Язык: Английский

Процитировано

21
Bone-targeting exosome nanoparticles activate Keap1 / Nrf2 / GPX4 signaling pathway to induce ferroptosis in osteosarcoma cells DOI Creative Commons
Wenkai Chen,

Zongguang Li,

Naichun Yu

и другие.

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Сен. 30, 2023

In recent years, the development of BMSCs-derived exosomes (EXO) for treatment osteosarcoma (OS) is a safe and promising modality OS treatment, which can effectively deliver drugs to tumor cells in vivo. However, differences carried, binding EXOs other organs limit their therapeutic efficacy. Therefore, improving OS-targeting ability BMSCs developing new crucial clinical application targeted therapy OS.In this study, we constructed potential nano platform by modifying using bone-targeting peptide SDSSD encapsulated capreomycin (CAP) within shell. These nanoparticles (NPs) showed homologous targeting (BT-EXO) significantly promotes cellular endocytosis vitro accumulation Furthermore, our results revealed that NPs induced ferroptosis prompting excessive reactive oxygen species (ROS), Fe2+ aggregation, lipid peroxidation further identified anticancer molecular mechanism as transduced Keap1/Nrf2/GPX4 signaling pathway. Also, these NP-directed significant inhibition growth vivo with no side effects.These suggest have superior activity mouse models vivo, providing strategy combining ferroptosis-based chemotherapy OS.

Язык: Английский

Процитировано

26
YTHDC1 as a tumor progression suppressor through modulating FSP1-dependent ferroptosis suppression in lung cancer DOI
Shuai Yuan,

Shu Xi,

Hong Weng

и другие.

Cell Death and Differentiation, Год журнала: 2023, Номер 30(12), С. 2477 - 2490

Опубликована: Окт. 30, 2023

Язык: Английский

Процитировано

26
Emerging roles of mitochondrial functions and epigenetic changes in the modulation of stem cell fate DOI Open Access
Chen‐Song Zhang, Yang Meng, Junhong Han

и другие.

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Янв. 12, 2024

Язык: Английский

Процитировано

16
Epigenetic modification of ferroptosis by non-coding RNAs in cancer drug resistance DOI Creative Commons
Hongquan Wang, Joshua S. Fleishman,

Sihang Cheng

и другие.

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Авг. 27, 2024

Abstract The development of drug resistance remains a major challenge in cancer treatment. Ferroptosis, unique type regulated cell death, plays pivotal role inhibiting tumour growth, presenting new opportunities treating chemotherapeutic resistance. Accumulating studies indicate that epigenetic modifications by non-coding RNAs (ncRNA) can determine vulnerability to ferroptosis. In this review, we first summarize the growth/development. Then, core molecular mechanisms ferroptosis, its upstream regulation, and downstream effects on Finally, review recent advances understanding how ncRNAs regulate ferroptosis from such modulate This aims enhance general ncRNA-mediated regulatory which highlighting ncRNA-ferroptosis axis as key druggable target overcoming

Язык: Английский

Процитировано

16
PRDX6 contributes to selenocysteine metabolism and ferroptosis resistance DOI Creative Commons
Zhiyi Chen, Alex Inague, Kamini Kaushal

и другие.

Molecular Cell, Год журнала: 2024, Номер 84(23), С. 4645 - 4659.e9

Опубликована: Ноя. 14, 2024

Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention begins with the uptake of Sec carrier, selenoprotein P (SELENOP). Following uptake, released from SELENOP metabolized via selenocysteine lyase (SCLY), producing selenide, a substrate selenophosphate synthetase 2 (SEPHS2), which provides essential selenium donor, (H2SePO3-), biosynthesis Sec-tRNA. Here, we discovered an alternative pathway in mediated by peroxiredoxin 6 (PRDX6), independent SCLY. Mechanistically, demonstrate that PRDX6 can readily react selenide interact SEPHS2, potentially acting as delivery system. Moreover, functional significance this route human cancer cells, revealing notable association between elevated expression MYCN-amplified neuroblastoma subtype. Our study sheds light on previously unrecognized aspect its implications ferroptosis, offering further possibilities therapeutic exploitation.

Язык: Английский

Процитировано

14