Qi Wang, Haofeng Wu, Zhaoyi Zhai, Dongliang Fang, Chun Yang, Li Liu, Xiaowei Jia, Baopu Du, Yingqi Lyu, Mingshan Zhang, Tao Lu, Lulu Wang, Yan Gao
{"title":"SPANXB1通过MMP1调控驱动乳腺癌脑转移：二甲双胍的潜在治疗见解","authors":"Qi Wang, Haofeng Wu, Zhaoyi Zhai, Dongliang Fang, Chun Yang, Li Liu, Xiaowei Jia, Baopu Du, Yingqi Lyu, Mingshan Zhang, Tao Lu, Lulu Wang, Yan Gao","doi":"10.1038/s41420-025-02721-4","DOIUrl":null,"url":null,"abstract":"<p><p>Cancer-testicular antigens (CTAs) have been considered as potential prognostic biomarkers and therapeutic targets due to their specific expression and roles in tumorigenesis and metastasis. Among these, the function and mechanism of SPANXB1 in breast cancer brain metastasis (BCBM) remain poorly understood. In this study, we investigated the role of SPANXB1 in BCBM. Our results demonstrated that SPANXB1 was highly expressed in brain-tropic breast cancer cells and brain metastasis samples. Functional assays revealed that SPANXB1 promoted breast cancer cell invasion, migration, vasculogenic mimicry (VM) formation, and blood-brain barrier (BBB) extravasation, thereby accelerating the process of brain metastasis. Mechanistically, SPANXB1 facilitated chromatin opening at the MMP1 promoter region via histone H3R17me2 modification and upregulated transcription factor YY1, leading to increased MMP1 expression. In vivo experiments further confirmed the role of SPANXB1 in enhancing brain metastasis. Notably, metformin effectively inhibited the expression of SPANXB1 and MMP1, thereby attenuating BCBM progression. The present study indicates the potential of SPANXB1 as a diagnostic and therapeutic target for BCBM. Additionally, our findings suggest metformin as a promising therapeutic strategy for this highly aggressive disease.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"418"},"PeriodicalIF":7.0000,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398519/pdf/","citationCount":"0","resultStr":"{\"title\":\"SPANXB1 drives brain metastasis in breast cancer via MMP1 regulation: potential therapeutic insights with metformin.\",\"authors\":\"Qi Wang, Haofeng Wu, Zhaoyi Zhai, Dongliang Fang, Chun Yang, Li Liu, Xiaowei Jia, Baopu Du, Yingqi Lyu, Mingshan Zhang, Tao Lu, Lulu Wang, Yan Gao\",\"doi\":\"10.1038/s41420-025-02721-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cancer-testicular antigens (CTAs) have been considered as potential prognostic biomarkers and therapeutic targets due to their specific expression and roles in tumorigenesis and metastasis. Among these, the function and mechanism of SPANXB1 in breast cancer brain metastasis (BCBM) remain poorly understood. In this study, we investigated the role of SPANXB1 in BCBM. Our results demonstrated that SPANXB1 was highly expressed in brain-tropic breast cancer cells and brain metastasis samples. Functional assays revealed that SPANXB1 promoted breast cancer cell invasion, migration, vasculogenic mimicry (VM) formation, and blood-brain barrier (BBB) extravasation, thereby accelerating the process of brain metastasis. Mechanistically, SPANXB1 facilitated chromatin opening at the MMP1 promoter region via histone H3R17me2 modification and upregulated transcription factor YY1, leading to increased MMP1 expression. In vivo experiments further confirmed the role of SPANXB1 in enhancing brain metastasis. Notably, metformin effectively inhibited the expression of SPANXB1 and MMP1, thereby attenuating BCBM progression. The present study indicates the potential of SPANXB1 as a diagnostic and therapeutic target for BCBM. Additionally, our findings suggest metformin as a promising therapeutic strategy for this highly aggressive disease.</p>\",\"PeriodicalId\":9735,\"journal\":{\"name\":\"Cell Death Discovery\",\"volume\":\"11 1\",\"pages\":\"418\"},\"PeriodicalIF\":7.0000,\"publicationDate\":\"2025-08-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398519/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Death Discovery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41420-025-02721-4\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02721-4","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
SPANXB1 drives brain metastasis in breast cancer via MMP1 regulation: potential therapeutic insights with metformin.
Cancer-testicular antigens (CTAs) have been considered as potential prognostic biomarkers and therapeutic targets due to their specific expression and roles in tumorigenesis and metastasis. Among these, the function and mechanism of SPANXB1 in breast cancer brain metastasis (BCBM) remain poorly understood. In this study, we investigated the role of SPANXB1 in BCBM. Our results demonstrated that SPANXB1 was highly expressed in brain-tropic breast cancer cells and brain metastasis samples. Functional assays revealed that SPANXB1 promoted breast cancer cell invasion, migration, vasculogenic mimicry (VM) formation, and blood-brain barrier (BBB) extravasation, thereby accelerating the process of brain metastasis. Mechanistically, SPANXB1 facilitated chromatin opening at the MMP1 promoter region via histone H3R17me2 modification and upregulated transcription factor YY1, leading to increased MMP1 expression. In vivo experiments further confirmed the role of SPANXB1 in enhancing brain metastasis. Notably, metformin effectively inhibited the expression of SPANXB1 and MMP1, thereby attenuating BCBM progression. The present study indicates the potential of SPANXB1 as a diagnostic and therapeutic target for BCBM. Additionally, our findings suggest metformin as a promising therapeutic strategy for this highly aggressive disease.
期刊介绍：
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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