• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

瞬时受体电位阳离子通道M2（TRPM2）介导活性氧诱导的前列腺癌细胞肌动蛋白重塑和细胞迁移。

TRPM2 channels mediate ROS-induced actin remodeling and cell migration of prostate cancer cells.

作者信息

Qi Pengwei, Zhao Jingting, Zhang Hongtian, Liu Xingyu, You Qing, Niu Jianguo, Ye Xiangming, Li Fangfang

机构信息

Department of Rehabilitation Medicine, Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.

Department of Biophysics, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

BMC Cancer. 2025 May 28;25(1):956. doi: 10.1186/s12885-025-14333-3.

DOI:10.1186/s12885-025-14333-3
PMID:40437388
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12117773/
Abstract

BACKGROUND

Actin remodeling plays important roles in pathophysiological processes such as cancer metastasis and angiogenesis. Reactive oxygen species (ROS) are signaling molecules thought to regulate cell migration by remodeling actin cytoskeleton. Earlier, we demonstrated that Transient receptor potential melastatin 2 (TRPM2) channels mediates HO-induced actin remodeling and cell migration in HeLa cells by manipulating Ca and Zn. However, the mechanism by which ROS produced in models more relevant to pathophysiological circumstances affect the actin cytoskeleton, remains poorly unknown. Therefore, this study aimed to explore the effect of ROS produced from pathophysiological conditions on actin cytoskeleton and cell migration. And then investigates the role of TRPM2 channels in the regulation of these types of ROS-induced actin remodeling and cell migration in prostate cancer cells.

METHODS

The study utilized various molecular probes, reagents, and cell culture techniques. Prostate cancer (PC)-3 and DU145 cell line were cultured and treated with different compounds to induce ROS production and actin remodeling. The actin cytoskeleton was stained with phalloidin or labelled with pActin-tdTomato plasmid and imaged using confocal microscopy. Zn and Ca levels were measured by Fluozin3-AM and Fluo4-AM probes respectively. Cell migration as-says were performed to assess the role of TRPM2 channels.

RESULTS

We demonstrated that both HO and palmitate induces TRPM2-dependent elevation of cytosolic Ca and Zn, leading to actin remodeling both in PC-3 and DU145 cells. Inhibition or knockdown of TRPM2 channels or chelation of Zn significantly reduced these effects.

CONCLUSIONS

TRPM2 channels and TRPM2-mediated Zn are essential in ROS-induced actin remodeling and cell migration in prostate cancer cells. Preventing TRPM2 channel activation and chelating Zn may offer potential therapeutic strategies for preventing cancer metastasis. Further research is needed to identify molecular targets of Zn in the actin cytoskeleton and cancer cell migration.

摘要

背景

肌动蛋白重塑在癌症转移和血管生成等病理生理过程中发挥着重要作用。活性氧（ROS）是被认为通过重塑肌动蛋白细胞骨架来调节细胞迁移的信号分子。此前，我们证明瞬时受体电位香草酸亚型2（TRPM2）通道通过操纵钙和锌介导HeLa细胞中过氧化氢（HO）诱导的肌动蛋白重塑和细胞迁移。然而，在更符合病理生理情况的模型中产生的ROS影响肌动蛋白细胞骨架的机制仍然知之甚少。因此，本研究旨在探讨病理生理条件下产生的ROS对肌动蛋白细胞骨架和细胞迁移的影响。然后研究TRPM2通道在调节前列腺癌细胞中这类ROS诱导的肌动蛋白重塑和细胞迁移中的作用。

方法

本研究使用了各种分子探针、试剂和细胞培养技术。培养前列腺癌（PC）-3和DU145细胞系，并用不同化合物处理以诱导ROS产生和肌动蛋白重塑。用鬼笔环肽对肌动蛋白细胞骨架进行染色，或用pActin-tdTomato质粒进行标记，并用共聚焦显微镜成像。分别用Fluozin3-AM和Fluo4-AM探针测量锌和钙水平。进行细胞迁移实验以评估TRPM2通道的作用。

结果

我们证明HO和棕榈酸酯均诱导TRPM2依赖的胞质钙和锌升高，导致PC-3和DU145细胞中的肌动蛋白重塑。抑制或敲低TRPM2通道或螯合锌可显著降低这些作用。

结论

TRPM2通道和TRPM2介导的锌在前列腺癌细胞中ROS诱导的肌动蛋白重塑和细胞迁移中至关重要。阻止TRPM2通道激活和螯合锌可能为预防癌症转移提供潜在的治疗策略。需要进一步研究以确定锌在肌动蛋白细胞骨架和癌细胞迁移中的分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/5eaa41ec8a13/12885_2025_14333_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/c14418d75796/12885_2025_14333_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/ce3693cd5e46/12885_2025_14333_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/fd24b56250a6/12885_2025_14333_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/71a43690f4eb/12885_2025_14333_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/a5276646dbde/12885_2025_14333_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/528c59dffecf/12885_2025_14333_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/57367ed9b237/12885_2025_14333_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/5eaa41ec8a13/12885_2025_14333_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/c14418d75796/12885_2025_14333_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/ce3693cd5e46/12885_2025_14333_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/fd24b56250a6/12885_2025_14333_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/71a43690f4eb/12885_2025_14333_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/a5276646dbde/12885_2025_14333_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/528c59dffecf/12885_2025_14333_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/57367ed9b237/12885_2025_14333_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d466/12117773/5eaa41ec8a13/12885_2025_14333_Fig8_HTML.jpg

相似文献

1
TRPM2 channels mediate ROS-induced actin remodeling and cell migration of prostate cancer cells.瞬时受体电位阳离子通道M2（TRPM2）介导活性氧诱导的前列腺癌细胞肌动蛋白重塑和细胞迁移。
BMC Cancer. 2025 May 28;25(1):956. doi: 10.1186/s12885-025-14333-3.
2
Reciprocal regulation of actin cytoskeleton remodelling and cell migration by Ca2+ and Zn2+: role of TRPM2 channels.Ca2+和Zn2+对肌动蛋白细胞骨架重塑和细胞迁移的相互调节：TRPM2通道的作用
J Cell Sci. 2016 May 15;129(10):2016-29. doi: 10.1242/jcs.179796. Epub 2016 Apr 11.
3
A critical role of the transient receptor potential melastatin 2 channel in a positive feedback mechanism for reactive oxygen species-induced delayed cell death.瞬时受体电位 melastatin 2 通道在活性氧诱导的延迟细胞死亡的正反馈机制中起关键作用。
J Cell Physiol. 2019 Apr;234(4):3647-3660. doi: 10.1002/jcp.27134. Epub 2018 Sep 19.
4
Signalling mechanisms mediating Zn-induced TRPM2 channel activation and cell death in microglial cells.介导 Zn 诱导的 TRPM2 通道激活和小胶质细胞死亡的信号机制。
Sci Rep. 2017 Mar 21;7:45032. doi: 10.1038/srep45032.
5
Serotonin and chronic hypoxic pulmonary hypertension activate a NADPH oxidase 4 and TRPM2 dependent pathway for pulmonary arterial smooth muscle cell proliferation and migration.血清素和慢性低氧性肺动脉高血压激活了一个 NADPH 氧化酶 4 和 TRPM2 依赖的通路，导致肺动脉平滑肌细胞增殖和迁移。
Vascul Pharmacol. 2021 Jun;138:106860. doi: 10.1016/j.vph.2021.106860. Epub 2021 Mar 29.
6
TRPM2-mediated rise in mitochondrial Zn promotes palmitate-induced mitochondrial fission and pancreatic β-cell death in rodents.TRPM2 介导线粒体 Zn 内流促进棕榈酸诱导的线粒体分裂和啮齿动物胰岛β细胞死亡。
Cell Death Differ. 2017 Dec;24(12):1999-2012. doi: 10.1038/cdd.2017.118. Epub 2017 Jul 28.
7
Facilitation of H2O2-induced A172 human glioblastoma cell death by insertion of oxidative stress-sensitive TRPM2 channels.通过插入氧化应激敏感的TRPM2通道促进H2O2诱导的A172人胶质母细胞瘤细胞死亡。
Anticancer Res. 2007 Nov-Dec;27(6B):3987-92.
8
Crosstalk Between Vascular Redox and Calcium Signaling in Hypertension Involves TRPM2 (Transient Receptor Potential Melastatin 2) Cation Channel.高血压中血管氧化还原与钙信号的串扰涉及 TRPM2（瞬时受体电位 melastatin 2）阳离子通道。
Hypertension. 2020 Jan;75(1):139-149. doi: 10.1161/HYPERTENSIONAHA.119.13861. Epub 2019 Nov 18.
9
Free fatty acid-induced HO activates TRPM2 to aggravate endothelial insulin resistance via Ca-dependent PERK/ATF4/TRB3 cascade in obese mice.游离脂肪酸诱导的 HO 通过 Ca 依赖性 PERK/ATF4/TRB3 级联激活 TRPM2 加重肥胖小鼠内皮胰岛素抵抗。
Free Radic Biol Med. 2019 Nov 1;143:288-299. doi: 10.1016/j.freeradbiomed.2019.08.018. Epub 2019 Aug 21.
10
TRPM2-mediated intracellular Zn2+ release triggers pancreatic β-cell death.瞬时受体电位阳离子通道M2型（TRPM2）介导的细胞内锌离子释放引发胰腺β细胞死亡。
Biochem J. 2015 Mar 15;466(3):537-46. doi: 10.1042/BJ20140747.

本文引用的文献

1
The activated CD36-Src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment.激活的 CD36-Src 轴促进高脂肪环境中肺腺癌细胞的增殖和肌动蛋白重塑相关转移。
Cell Death Dis. 2023 Aug 23;14(8):548. doi: 10.1038/s41419-023-06078-3.
2
Calcium signalling pathways in prostate cancer initiation and progression.前列腺癌发生和进展中的钙信号通路。
Nat Rev Urol. 2023 Sep;20(9):524-543. doi: 10.1038/s41585-023-00738-x. Epub 2023 Mar 24.
3
A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling.
富含棕榈酸的转移灶微环境通过 p65 乙酰化促进转移生长，从而导致促转移的 NF-κB 信号通路激活。
Nat Cancer. 2023 Mar;4(3):344-364. doi: 10.1038/s43018-023-00513-2. Epub 2023 Feb 2.
4
The human ion channel TRPM2 modulates migration and invasion in neuroblastoma through regulation of integrin expression.人类离子通道 TRPM2 通过调节整合素表达来调节神经母细胞瘤的迁移和侵袭。
Sci Rep. 2022 Nov 29;12(1):20544. doi: 10.1038/s41598-022-25138-w.
5
TRPM8 as an Anti-Tumoral Target in Prostate Cancer Growth and Metastasis Dissemination.TRPM8 作为前列腺癌生长和转移扩散的抗肿瘤靶标。
Int J Mol Sci. 2022 Jun 15;23(12):6672. doi: 10.3390/ijms23126672.
6
Hyperglycemia induces gastric carcinoma proliferation and migration via the Pin1/BRD4 pathway.高血糖通过Pin1/BRD4途径诱导胃癌增殖和迁移。
Cell Death Discov. 2022 Apr 23;8(1):224. doi: 10.1038/s41420-022-01030-4.
7
The Plasma Membrane Ca Pump PMCA4b Regulates Melanoma Cell Migration through Remodeling of the Actin Cytoskeleton.质膜钙泵PMCA4b通过重塑肌动蛋白细胞骨架调节黑色素瘤细胞迁移。
Cancers (Basel). 2021 Mar 17;13(6):1354. doi: 10.3390/cancers13061354.
8
The Discovery of Novel ACA Derivatives as Specific TRPM2 Inhibitors that Reduce Ischemic Injury Both In Vitro and In Vivo.新型 ACA 衍生物作为特异性 TRPM2 抑制剂的发现可减少体外和体内的缺血性损伤。
J Med Chem. 2021 Apr 8;64(7):3976-3996. doi: 10.1021/acs.jmedchem.0c02129. Epub 2021 Mar 30.
9
Zn influx activates ERK and Akt signaling pathways.锌内流激活 ERK 和 Akt 信号通路。
Proc Natl Acad Sci U S A. 2021 Mar 16;118(11). doi: 10.1073/pnas.2015786118.
10
Palmitate-Induced IRE1-XBP1-ZEB Signaling Represses Desmoplakin Expression and Promotes Cancer Cell Migration.棕榈酸诱导的 IRE1-XBP1-ZEB 信号抑制桥粒芯蛋白表达并促进癌细胞迁移。
Mol Cancer Res. 2021 Feb;19(2):240-248. doi: 10.1158/1541-7786.MCR-19-0480. Epub 2020 Oct 26.