{"title":"玉米赤霉烯酮通过激活雌激素受体介导的 Rho/ROCK/PMLC 信号通路促进子宫内膜癌细胞迁移和侵袭。","authors":"","doi":"10.1016/j.fct.2024.115017","DOIUrl":null,"url":null,"abstract":"<div><div>Zearalenone (ZEA), has emerged as a potential endocrine-disrupting chemical (EDC). Previous results show ZEA effects on endometrial stromal cell apoptosis, migration, and growth of endometriosis. Despite the reported presence of ZEA in Endometrial Cancer (EC) patient's blood and tissues, ZEA-induced EC promotion and its mechanism/s remain elusive. In this study, Ishikawa cells were used to investigate the ZEA effects on Ishikawa cell migration, invasion, and the underlying mechanism involved in these events. Ishikawa cells were exposed to low concentrations of ZEA (5, 25, and 125 nM) for 48 h, and morphological alterations, migration, invasion, markers associated with epithelial-mesenchymal transition (EMT), E-cadherin, Vimentin, RhoA/ROCK/PMLC pathway activation were analyzed. ZEA (25 nM) exposure caused morphological alterations like stress fiber, filopodia formation, loss of cell adhesion, and a significant increase in migration and invasive potential in extracellular matrix-coated porous membranes. Moreover, ZEA exposure also increases the Rho-GTPase activity and expression of pathway mediators, GEFH1, RhoA, ROCK1+2, CDC42, and PMLC/MLC. Furthermore, pre-treatment with specific pharmacological inhibitors for Estrogen receptor-alpha (ER-α) and ROCK attenuate the ZEA-induced stress fiber formation and altered expression of E-cadherin, Vimentin, and Rho/ROCK/PMLC pathway mediators. These findings suggest that Rho/ROCK/PMLC signaling pathways are involved in ZEA-induced Ishikawa cell migration and invasion.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Zearalenone promotes endometrial cancer cell migration and invasion via activation of estrogen receptor-mediated Rho/ROCK/PMLC signaling pathway\",\"authors\":\"\",\"doi\":\"10.1016/j.fct.2024.115017\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Zearalenone (ZEA), has emerged as a potential endocrine-disrupting chemical (EDC). Previous results show ZEA effects on endometrial stromal cell apoptosis, migration, and growth of endometriosis. Despite the reported presence of ZEA in Endometrial Cancer (EC) patient's blood and tissues, ZEA-induced EC promotion and its mechanism/s remain elusive. In this study, Ishikawa cells were used to investigate the ZEA effects on Ishikawa cell migration, invasion, and the underlying mechanism involved in these events. Ishikawa cells were exposed to low concentrations of ZEA (5, 25, and 125 nM) for 48 h, and morphological alterations, migration, invasion, markers associated with epithelial-mesenchymal transition (EMT), E-cadherin, Vimentin, RhoA/ROCK/PMLC pathway activation were analyzed. ZEA (25 nM) exposure caused morphological alterations like stress fiber, filopodia formation, loss of cell adhesion, and a significant increase in migration and invasive potential in extracellular matrix-coated porous membranes. Moreover, ZEA exposure also increases the Rho-GTPase activity and expression of pathway mediators, GEFH1, RhoA, ROCK1+2, CDC42, and PMLC/MLC. Furthermore, pre-treatment with specific pharmacological inhibitors for Estrogen receptor-alpha (ER-α) and ROCK attenuate the ZEA-induced stress fiber formation and altered expression of E-cadherin, Vimentin, and Rho/ROCK/PMLC pathway mediators. These findings suggest that Rho/ROCK/PMLC signaling pathways are involved in ZEA-induced Ishikawa cell migration and invasion.</div></div>\",\"PeriodicalId\":317,\"journal\":{\"name\":\"Food and Chemical Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Food and Chemical Toxicology\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0278691524005830\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"FOOD SCIENCE & TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Food and Chemical Toxicology","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0278691524005830","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"FOOD SCIENCE & TECHNOLOGY","Score":null,"Total":0}
Zearalenone promotes endometrial cancer cell migration and invasion via activation of estrogen receptor-mediated Rho/ROCK/PMLC signaling pathway
Zearalenone (ZEA), has emerged as a potential endocrine-disrupting chemical (EDC). Previous results show ZEA effects on endometrial stromal cell apoptosis, migration, and growth of endometriosis. Despite the reported presence of ZEA in Endometrial Cancer (EC) patient's blood and tissues, ZEA-induced EC promotion and its mechanism/s remain elusive. In this study, Ishikawa cells were used to investigate the ZEA effects on Ishikawa cell migration, invasion, and the underlying mechanism involved in these events. Ishikawa cells were exposed to low concentrations of ZEA (5, 25, and 125 nM) for 48 h, and morphological alterations, migration, invasion, markers associated with epithelial-mesenchymal transition (EMT), E-cadherin, Vimentin, RhoA/ROCK/PMLC pathway activation were analyzed. ZEA (25 nM) exposure caused morphological alterations like stress fiber, filopodia formation, loss of cell adhesion, and a significant increase in migration and invasive potential in extracellular matrix-coated porous membranes. Moreover, ZEA exposure also increases the Rho-GTPase activity and expression of pathway mediators, GEFH1, RhoA, ROCK1+2, CDC42, and PMLC/MLC. Furthermore, pre-treatment with specific pharmacological inhibitors for Estrogen receptor-alpha (ER-α) and ROCK attenuate the ZEA-induced stress fiber formation and altered expression of E-cadherin, Vimentin, and Rho/ROCK/PMLC pathway mediators. These findings suggest that Rho/ROCK/PMLC signaling pathways are involved in ZEA-induced Ishikawa cell migration and invasion.
期刊介绍:
Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs.
The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following:
-Adverse physiological/biochemical, or pathological changes induced by specific defined substances
-New techniques for assessing potential toxicity, including molecular biology
-Mechanisms underlying toxic phenomena
-Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability.
Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.