{"title":"HGF/c-Met通过EZH2/HOTAIR-miR-141/200a反馈信号通路促进乳腺癌他莫昔芬耐药","authors":"Xiaofeng Lai, Yuan Zhang, Mengyang Li, Shentong Yu, Shuiliang Wang, Shenghang Zhang, Huimin Niu, Li Chen, Xiaopeng Lan, Jian Zhang, Suning Chen","doi":"10.1002/mc.23878","DOIUrl":null,"url":null,"abstract":"<p><p>Tamoxifen is one of the most frequently used endocrine medications for the treatment of estrogen receptor-positive (ER + ) breast cancer (BC). Unfortunately, tamoxifen resistance (TR) brings more challenges to the clinical treatment, and the mechanisms of TR have not yet been fully clarified. HGF/c-Met is closely associated with cancer metastasis, but whether it is involved in TR remains unclear. In our study, we found that the activation of HGF/c-Met was crucial for TR maintenance. Synergistic interaction with HOTAIR and EZH2 accelerated HGF expression by repressing miR-141/200a. Additionally, HGF/c-Met activated NF-κB, forming a positive feedback loop of EZH2/HOTAIR-miR-141/200a-HGF/c-Met-NF-κB. Our findings indicated that HGF/c-Met functioned as an important biomarker for TR, and HGF/c-Met inhibition provided a novel approach to TR treatment.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"769-783"},"PeriodicalIF":3.0000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"HGF/c-Met Promotes Breast Cancer Tamoxifen Resistance Through the EZH2/HOTAIR-miR-141/200a Feedback Signaling Pathway.\",\"authors\":\"Xiaofeng Lai, Yuan Zhang, Mengyang Li, Shentong Yu, Shuiliang Wang, Shenghang Zhang, Huimin Niu, Li Chen, Xiaopeng Lan, Jian Zhang, Suning Chen\",\"doi\":\"10.1002/mc.23878\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Tamoxifen is one of the most frequently used endocrine medications for the treatment of estrogen receptor-positive (ER + ) breast cancer (BC). Unfortunately, tamoxifen resistance (TR) brings more challenges to the clinical treatment, and the mechanisms of TR have not yet been fully clarified. HGF/c-Met is closely associated with cancer metastasis, but whether it is involved in TR remains unclear. In our study, we found that the activation of HGF/c-Met was crucial for TR maintenance. Synergistic interaction with HOTAIR and EZH2 accelerated HGF expression by repressing miR-141/200a. Additionally, HGF/c-Met activated NF-κB, forming a positive feedback loop of EZH2/HOTAIR-miR-141/200a-HGF/c-Met-NF-κB. Our findings indicated that HGF/c-Met functioned as an important biomarker for TR, and HGF/c-Met inhibition provided a novel approach to TR treatment.</p>\",\"PeriodicalId\":19003,\"journal\":{\"name\":\"Molecular Carcinogenesis\",\"volume\":\" \",\"pages\":\"769-783\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Carcinogenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/mc.23878\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Carcinogenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/mc.23878","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/24 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
HGF/c-Met Promotes Breast Cancer Tamoxifen Resistance Through the EZH2/HOTAIR-miR-141/200a Feedback Signaling Pathway.
Tamoxifen is one of the most frequently used endocrine medications for the treatment of estrogen receptor-positive (ER + ) breast cancer (BC). Unfortunately, tamoxifen resistance (TR) brings more challenges to the clinical treatment, and the mechanisms of TR have not yet been fully clarified. HGF/c-Met is closely associated with cancer metastasis, but whether it is involved in TR remains unclear. In our study, we found that the activation of HGF/c-Met was crucial for TR maintenance. Synergistic interaction with HOTAIR and EZH2 accelerated HGF expression by repressing miR-141/200a. Additionally, HGF/c-Met activated NF-κB, forming a positive feedback loop of EZH2/HOTAIR-miR-141/200a-HGF/c-Met-NF-κB. Our findings indicated that HGF/c-Met functioned as an important biomarker for TR, and HGF/c-Met inhibition provided a novel approach to TR treatment.
期刊介绍：
Molecular Carcinogenesis publishes articles describing discoveries in basic and clinical science of the mechanisms involved in chemical-, environmental-, physical (e.g., radiation, trauma)-, infection and inflammation-associated cancer development, basic mechanisms of cancer prevention and therapy, the function of oncogenes and tumors suppressors, and the role of biomarkers for cancer risk prediction, molecular diagnosis and prognosis.
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