Knockdown of ENO1 promotes autophagy dependent-ferroptosis and suppresses glycolysis in breast cancer cells via the regulation of CST1

IF 3.5 4区 医学 Q2 CHEMISTRY, MEDICINAL Drug Development Research Pub Date : 2024-11-06 DOI:10.1002/ddr.70004
Guoliang Huang, Lian Lu, Yuhong You, Jie Li, Kaixiang Zhang
{"title":"Knockdown of ENO1 promotes autophagy dependent-ferroptosis and suppresses glycolysis in breast cancer cells via the regulation of CST1","authors":"Guoliang Huang,&nbsp;Lian Lu,&nbsp;Yuhong You,&nbsp;Jie Li,&nbsp;Kaixiang Zhang","doi":"10.1002/ddr.70004","DOIUrl":null,"url":null,"abstract":"<p>Autophagy-dependent ferroptosis and glycolysis play a significant role in tumor development. α-Enolase (ENO1), a glycolytic enzyme, has been demonstrated to function as a crucial modulator in breast cancer (BC). However, the specific mechanism by which ENO1 influences the ferroptosis and glycolysis of BC remains unclear. qRT-PCR, along with western blot analysis was applied to investigate ENO1 and cystatin SN (CST1) expression in BC cells. Glycolysis level was measured by extracellular acidification rate (ECAR), lactate production, glucose consumption, and western blot analysis. Ferroptosis was evaluated by iron and lipid peroxidation assay, DCFH-DA staining, and western blot analysis. Immunofluorescence, together with western blot analysis was adopted for assessing cell autophagy and mTOR signaling pathway. Cell apoptosis and Ki67 level were measured by TUNEL and immunohistochemistry, respectively. ENO1 had abundant existence in BC cell lines. ENO1 silencing inhibited glycolysis but promoted ferroptosis and autophagy. In addition, autophagy inhibitor 3-MA reversed the impacts of ENO1 silencing on glycolysis and ferroptosis. Meanwhile, mTOR activator MHY1485 demonstrated opposing effects on autophagy. Moreover, CST1 could be extensively found in BC cell lines, and its overexpression reversed the effects of ENO1 silencing on glycolysis and ferroptosis. In vivo experiments illustrated that ENO1 deletion suppressed BC tumor growth, increased the apoptosis rate, restrained cell proliferation, and glycolysis, but promoted ferroptosis and autophagy, as well as reducing CST1 and mTOR signaling. To sum up, ENO1 silencing mediated a utophagy-dependent ferroptosis and glycolysis in BC cells by regulating CST1.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Development Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ddr.70004","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

Autophagy-dependent ferroptosis and glycolysis play a significant role in tumor development. α-Enolase (ENO1), a glycolytic enzyme, has been demonstrated to function as a crucial modulator in breast cancer (BC). However, the specific mechanism by which ENO1 influences the ferroptosis and glycolysis of BC remains unclear. qRT-PCR, along with western blot analysis was applied to investigate ENO1 and cystatin SN (CST1) expression in BC cells. Glycolysis level was measured by extracellular acidification rate (ECAR), lactate production, glucose consumption, and western blot analysis. Ferroptosis was evaluated by iron and lipid peroxidation assay, DCFH-DA staining, and western blot analysis. Immunofluorescence, together with western blot analysis was adopted for assessing cell autophagy and mTOR signaling pathway. Cell apoptosis and Ki67 level were measured by TUNEL and immunohistochemistry, respectively. ENO1 had abundant existence in BC cell lines. ENO1 silencing inhibited glycolysis but promoted ferroptosis and autophagy. In addition, autophagy inhibitor 3-MA reversed the impacts of ENO1 silencing on glycolysis and ferroptosis. Meanwhile, mTOR activator MHY1485 demonstrated opposing effects on autophagy. Moreover, CST1 could be extensively found in BC cell lines, and its overexpression reversed the effects of ENO1 silencing on glycolysis and ferroptosis. In vivo experiments illustrated that ENO1 deletion suppressed BC tumor growth, increased the apoptosis rate, restrained cell proliferation, and glycolysis, but promoted ferroptosis and autophagy, as well as reducing CST1 and mTOR signaling. To sum up, ENO1 silencing mediated a utophagy-dependent ferroptosis and glycolysis in BC cells by regulating CST1.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
敲除ENO1可通过调控CST1促进乳腺癌细胞的自噬依赖性铁变态反应并抑制糖酵解。
自噬依赖性铁蛋白沉积和糖酵解在肿瘤发生发展中起着重要作用。α-烯醇化酶(ENO1)是一种糖酵解酶,已被证实在乳腺癌(BC)中发挥着重要的调节作用。qRT-PCR和Western印迹分析被用来研究ENO1和胱抑素SN(CST1)在乳腺癌细胞中的表达。糖酵解水平通过细胞外酸化率(ECAR)、乳酸生成、葡萄糖消耗和 Western 印迹分析进行测量。通过铁和脂质过氧化测定、DCFH-DA 染色和 Western 印迹分析评估铁变态反应。免疫荧光和 Western 印迹分析用于评估细胞自噬和 mTOR 信号通路。细胞凋亡和Ki67水平分别通过TUNEL和免疫组化进行检测。ENO1在BC细胞系中大量存在。沉默ENO1可抑制糖酵解,但促进铁突变和自噬。此外,自噬抑制剂3-MA能逆转ENO1沉默对糖酵解和铁突变的影响。同时,mTOR 激活剂 MHY1485 对自噬的影响则相反。此外,CST1广泛存在于BC细胞系中,其过表达可逆转ENO1沉默对糖酵解和铁突变的影响。体内实验表明,ENO1缺失抑制了BC肿瘤的生长,增加了细胞凋亡率,抑制了细胞增殖和糖酵解,但促进了铁代谢和自噬,并减少了CST1和mTOR信号传导。综上所述,ENO1沉默通过调节CST1介导了依赖于吞噬细胞的铁代谢和糖酵解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
期刊最新文献
Knockdown of ENO1 promotes autophagy dependent-ferroptosis and suppresses glycolysis in breast cancer cells via the regulation of CST1 MLLT3 knockdown suppresses proliferation and cell mobility in human lung adenocarcinoma PARP7i Clinical Candidate RBN-2397 Exerts Antiviral Activity by Modulating Interferon-β Associated Innate Immune Response in Macrophages Targeted therapies for Glioblastoma multiforme (GBM): State-of-the-art and future prospects Agmatine: An Emerging Approach for Neuroprotection in Recurrent Ischemic Stroke Events in a Murine Model
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1