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。