Cancer-associated fibroblasts promote doxorubicin resistance in triple-negative breast cancer through enhancing ZFP64 histone lactylation to regulate ferroptosis DOI Creative Commons
Kejing Zhang, Lei Guo, Xin Li

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 28, 2025

Cancer-associated fibroblasts (CAFs) have been identified to drive chemotherapy resistance in triple-negative breast cancer (TNBC). This study evaluated the functions of CAFs-mediated suppressive ferroptosis doxorubicin (DOX) TNBC and its detailed molecular mechanisms. cell lines were co-cultured with CAFs isolated from DOX-sensitive (CAF/S) or DOX-resistant (CAF/R) tissues. Cell viability death assessed by counting Kit-8 (CCK-8) propidium iodide (PI) staining. Ferroptosis was detection Fe2+, malondialdehyde (MDA), glutathione (GSH), lipid reactive oxygen species (ROS) levels. Histone lactylation determined lactate production, pan-Kla H3K18la expression. Molecular mechanism chromatin immunoprecipitation (ChIP) dual luciferase reporter system. Molecule protein expression detected quantitative Real-Time PCR (RT-qPCR), Western blotting, immunofluorescence immunohistochemical cells injected into mammary fat pad nude mice investigate DOX sensitivity vivo. CAFs-derived repressed confer DOX. Moreover, zinc finger 64 (ZFP64) elevated associated high histone level. facilitated enhance ZFP64 expression, which triggered inhibition resistance. In addition, bound promoters GTP cyclohydrolase-1 (GCH1) ferritin heavy chain 1 (FTH1), thereby promoting their Rescue experiments indicated that silencing-induced could be counteracted GCH1 FTH1 overexpression. acted as a inhibitor cause via lactylation-mediated up-regulation subsequent promotion GCH1-induced peroxidation FTH1-induced intracellular Fe2+ consumption.

Language: Английский

Ce6-modified Fe ions-doped carbon dots as multifunctional nanoplatform for ferroptosis and photodynamic synergistic therapy of melanoma DOI Creative Commons
Haiqiu Li,

Yichen Dou,

Hang Yang

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 10, 2024

Abstract Background Despite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), lack efficient inducers poor solubility photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination cancers. Results Herein, an ferroptosis/PDT integrated nanoplatform is constructed based on chlorin e6-modified Fe ions-doped (Fe-CDs@Ce6). As a novel type iron-carbon hybrid nanoparticles, as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis inhibit migration mouse skin cells (B16), but have no toxicity normal cells. The nano-conjugated structures facilitate not only aqueous dispersibility Ce6, also self-accumulation ability Fe-CDs@Ce6 within area without requiring extra targets. Moreover, therapeutic effects synergistically enhanced due increased GSH depletion by PDT elevated singlet oxygen ( 1 O 2 ) production efficiency Fe-CDs. When combined with laser irradiation, tumor growth be significantly suppressed through cyclic administration. T -weighted magnetic resonance imaging (MRI) capability reveals potentials cancer diagnosis navigation therapy. Conclusions Our findings indicate multifunctionality in effectively combining therapy, targeting MRI imaging, which enables become promising biocompatible treatment melanoma. Graphic

Language: Английский

Citations

5
Ferroptosis: Molecular perspective, cellular influence, cancer manifestation, and therapeutic potentials DOI
Pawan Kumar Pandey,

Saurabh Bhorkade,

Shikha Jha

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 100, P. 105998 - 105998

Published: July 31, 2024

Language: Английский

Citations

5
Targeting PRMT3 impairs methylation and oligomerization of HSP60 to boost anti-tumor immunity by activating cGAS/STING signaling DOI Creative Commons

Yunxing Shi,

Zongfeng Wu,

Shaoru Liu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 10, 2024

Abstract Immune checkpoint blockade (ICB) has emerged as a promising therapeutic option for hepatocellular carcinoma (HCC), but resistance to ICB occurs and patient responses vary. Here, we uncover protein arginine methyltransferase 3 (PRMT3) driver immunotherapy in HCC. We show that PRMT3 expression is induced by ICB-activated T cells via an interferon-gamma (IFNγ)-STAT1 signaling pathway, higher levels correlate with reduced numbers of tumor-infiltrating CD8 + poorer response ICB. Genetic depletion or pharmacological inhibition elicits influx into tumors reduces tumor size HCC mouse models. Mechanistically, methylates HSP60 at R446 induce oligomerization maintain mitochondrial homeostasis. Targeting PRMT3-dependent methylation disrupts integrity increases DNA (mtDNA) leakage, which results cGAS/STING-mediated anti-tumor immunity. Lastly, blocking functions synergize PD-1 Our study thus identifies potential biomarker target overcome

Language: Английский

Citations

5
Identification of PRMT5 as a therapeutic target in cholangiocarcinoma DOI

Jasmin Elurbide,

Leticia Colyn, María U. Latasa

et al.

Gut, Journal Year: 2024, Volume and Issue: 74(1), P. 116 - 127

Published: Sept. 11, 2024

Cholangiocarcinoma (CCA) is a very difficult-to-treat cancer. Chemotherapies are little effective and response to immune checkpoint inhibitors limited. Therefore, new therapeutic strategies need be identified.

Language: Английский

Citations

4
MTA-cooperative PRMT5 inhibitors enhance T cell-mediated antitumor activity in MTAP-loss tumors DOI Creative Commons
Si Chen, Jiakai Hou, Roshni Jaffery

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(9), P. e009600 - e009600

Published: Sept. 1, 2024

Hyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining inhibitors (PRMT5i) with cancer immunotherapy. However, global suppression activity impairs effector functions cells. Here, we sought identify strategies specifically inhibit tissues and develop effective PRMT5i-based immuno-oncology (IO) combinations for treatment, particularly methylthioadenosine phosphorylase (MTAP)-loss cancer.

Language: Английский

Citations

4
Targeting PRMT5 through PROTAC for the treatment of triple-negative breast cancer DOI Creative Commons

Yaxun Guo,

Yuzhan Li, Zhongmei Zhou

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Nov. 30, 2024

Abstract Background Triple-negative breast cancer (TNBC) is currently the most aggressive subtype of cancer, characterized by high heterogeneity and strong invasiveness, lacks effective therapies. PRMT5, a type II protein arginine methyltransferase, upregulated in numerous cancers, including TNBC, plays critical role, marked it as an attractive therapeutic target. PROTAC (Proteolysis Targeting Chimeras) innovative drug development technology that utilizes ubiquitin-proteasome system (UPS) to degrade target proteins, which higher activity, enhanced safety, lower resistance, reduced toxicity, offering significant value for clinical translation. Methods This study develop potential degraders targeting PRMT5 vitro vivo. Results Through design, synthesis screening series targeted compounds, we identified YZ-836P compound exerted cytotoxic effects levels its key downstream KLF5 TNBC after 48 h. Its efficacy was significantly superior had been reported. induced G1 phase cell cycle arrest apoptosis cells. Additionally, demonstrated promoted ubiquitination degradation cereblon (CRBN)-dependent manner. Notably, exhibited pronounced inhibiting growth patient-derived organoids xenografts nude mice. Conclusions These findings position promising candidate advancing treatment modalities TNBC. Trial registration Ethics Committee Yunnan Cancer Hospital, KYCS2023-078. Registered 7 June 2023.

Language: Английский

Citations

4
Ferroptosis-related signaling pathways in cancer drug resistance DOI Open Access
Yang Yang‐Hartwich,

Simin Yu,

Wanyao Liu

et al.

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 6, 2025

Ferroptosis is an iron-dependent form of programmed cell death induced by lipid peroxidation. This process regulated signaling pathways associated with redox balance, iron metabolism, and metabolism. Cancer cells' increased demand makes them especially susceptible to ferroptosis, significantly influencing cancer development, therapeutic response, metastasis. Recent findings indicate that cells can evade ferroptosis downregulating key related this process, contributing drug resistance. underscores the possibility modulating as approach counteract resistance enhance efficacy. review outlines involved in their interactions cancer-related pathways. We also highlight current understanding resistance, offering insights into how targeting provide novel approaches for drug-resistant cancers. Finally, we explore potential ferroptosis-inducing compounds examine challenges opportunities development evolving field.

Language: Английский

Citations

0
Arginine and colorectal cancer: Exploring arginine-related therapeutic strategies and novel insights into cancer immunotherapies DOI
Ketao Jin, Xiufeng Chu, Jun Qian

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114146 - 114146

Published: Jan. 28, 2025

Language: Английский

Citations

0
Targeting Protein Arginine Methyltransferases in Breast Cancer: Promising Strategies DOI

Yuancheng Wei,

Xiaodan Lyu,

Wang Jia

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 992, P. 177350 - 177350

Published: Feb. 4, 2025

Language: Английский

Citations

0
Current Status and Future Directions of Ferroptosis Research in Breast Cancer: Bibliometric Analysis DOI Creative Commons
Jia‐Yuan Luo, Yu-Long Deng,

Sharon Lu

et al.

Interactive Journal of Medical Research, Journal Year: 2025, Volume and Issue: 14, P. e66286 - e66286

Published: Feb. 26, 2025

Background Ferroptosis, as a novel modality of cell death, holds significant potential in elucidating the pathogenesis and advancing therapeutic strategies for breast cancer. Objective This study aims to comprehensively analyze current ferroptosis research future trends, guiding cancer advancements innovative treatment strategies. Methods used R package Bibliometrix (Department Economic Statistical Sciences at University Naples Federico II), VOSviewer (Centre Science Technology Studies Leiden University), CiteSpace (Drexel University’s College Information Technology), conduct bibliometric analysis 387 papers on from Web Core Collection. The covers authors, institutions, journals, countries or regions, publication volumes, citations, keywords. Results number publications related this field has surged annually, with China United States collaborating closely leading output. Sun Yat-sen stands out among while journal Frontiers Oncology author Efferth T contribute significantly field. Highly cited within domain primarily focus induction ferroptosis, protein regulation, comparisons other modes providing foundation treatment. Keyword highlights maturity glutathione peroxidase 4-related research, subtypes emerging motor themes tumor microenvironment, immunotherapy, prognostic models identified basic themes. Furthermore, application nanoparticles serves an additional complement Conclusions status focuses exploration relevant theoretical mechanisms, whereas trends mechanisms emphasize investigation strategies, particularly clinical immunotherapy microenvironment. Nanotherapy demonstrated domain. Future directions should deepen accelerate translation findings provide new insights innovation development

Language: Английский

Citations

0