Pengwei Qi, Jingting Zhao, Hongtian Zhang, Xingyu Liu, Qing You, Jianguo Niu, Xiangming Ye, Fangfang Li
{"title":"TRPM2通道介导ros诱导的前列腺癌细胞肌动蛋白重构和细胞迁移。","authors":"Pengwei Qi, Jingting Zhao, Hongtian Zhang, Xingyu Liu, Qing You, Jianguo Niu, Xiangming Ye, Fangfang Li","doi":"10.1186/s12885-025-14333-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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 H<sub>2</sub>O<sub>2</sub>-induced actin remodeling and cell migration in HeLa cells by manipulating Ca<sup>2+</sup> and Zn<sup>2+</sup>. 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.</p><p><strong>Methods: </strong>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<sup>2+</sup> and Ca<sup>2+</sup> levels were measured by Fluozin3-AM and Fluo4-AM probes respectively. Cell migration as-says were performed to assess the role of TRPM2 channels.</p><p><strong>Results: </strong>We demonstrated that both H<sub>2</sub>O<sub>2</sub> and palmitate induces TRPM2-dependent elevation of cytosolic Ca<sup>2+</sup> and Zn<sup>2+</sup>, leading to actin remodeling both in PC-3 and DU145 cells. Inhibition or knockdown of TRPM2 channels or chelation of Zn<sup>2+</sup> significantly reduced these effects.</p><p><strong>Conclusions: </strong>TRPM2 channels and TRPM2-mediated Zn<sup>2+</sup> are essential in ROS-induced actin remodeling and cell migration in prostate cancer cells. Preventing TRPM2 channel activation and chelating Zn<sup>2+</sup> may offer potential therapeutic strategies for preventing cancer metastasis. Further research is needed to identify molecular targets of Zn<sup>2+</sup> in the actin cytoskeleton and cancer cell migration.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"956"},"PeriodicalIF":3.4000,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117773/pdf/","citationCount":"0","resultStr":"{\"title\":\"TRPM2 channels mediate ROS-induced actin remodeling and cell migration of prostate cancer cells.\",\"authors\":\"Pengwei Qi, Jingting Zhao, Hongtian Zhang, Xingyu Liu, Qing You, Jianguo Niu, Xiangming Ye, Fangfang Li\",\"doi\":\"10.1186/s12885-025-14333-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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 H<sub>2</sub>O<sub>2</sub>-induced actin remodeling and cell migration in HeLa cells by manipulating Ca<sup>2+</sup> and Zn<sup>2+</sup>. 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.</p><p><strong>Methods: </strong>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<sup>2+</sup> and Ca<sup>2+</sup> levels were measured by Fluozin3-AM and Fluo4-AM probes respectively. Cell migration as-says were performed to assess the role of TRPM2 channels.</p><p><strong>Results: </strong>We demonstrated that both H<sub>2</sub>O<sub>2</sub> and palmitate induces TRPM2-dependent elevation of cytosolic Ca<sup>2+</sup> and Zn<sup>2+</sup>, leading to actin remodeling both in PC-3 and DU145 cells. Inhibition or knockdown of TRPM2 channels or chelation of Zn<sup>2+</sup> significantly reduced these effects.</p><p><strong>Conclusions: </strong>TRPM2 channels and TRPM2-mediated Zn<sup>2+</sup> are essential in ROS-induced actin remodeling and cell migration in prostate cancer cells. Preventing TRPM2 channel activation and chelating Zn<sup>2+</sup> may offer potential therapeutic strategies for preventing cancer metastasis. Further research is needed to identify molecular targets of Zn<sup>2+</sup> in the actin cytoskeleton and cancer cell migration.</p>\",\"PeriodicalId\":9131,\"journal\":{\"name\":\"BMC Cancer\",\"volume\":\"25 1\",\"pages\":\"956\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-05-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117773/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12885-025-14333-3\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12885-025-14333-3","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
TRPM2 channels mediate ROS-induced actin remodeling and cell migration of prostate cancer cells.
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 H2O2-induced actin remodeling and cell migration in HeLa cells by manipulating Ca2+ and Zn2+. 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. Zn2+ and Ca2+ 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 H2O2 and palmitate induces TRPM2-dependent elevation of cytosolic Ca2+ and Zn2+, leading to actin remodeling both in PC-3 and DU145 cells. Inhibition or knockdown of TRPM2 channels or chelation of Zn2+ significantly reduced these effects.
Conclusions: TRPM2 channels and TRPM2-mediated Zn2+ are essential in ROS-induced actin remodeling and cell migration in prostate cancer cells. Preventing TRPM2 channel activation and chelating Zn2+ may offer potential therapeutic strategies for preventing cancer metastasis. Further research is needed to identify molecular targets of Zn2+ in the actin cytoskeleton and cancer cell migration.
期刊介绍：
BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
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