SPANXB1 drives brain metastasis in breast cancer via MMP1 regulation: potential therapeutic insights with metformin.

IF 7 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-08-30 DOI:10.1038/s41420-025-02721-4

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

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引用次数: 0

Abstract

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.

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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

癌睾丸抗原（cta）由于其在肿瘤发生和转移中的特异性表达和作用而被认为是潜在的预后生物标志物和治疗靶点。其中，SPANXB1在乳腺癌脑转移（BCBM）中的功能和机制尚不清楚。在这项研究中，我们研究了SPANXB1在BCBM中的作用。我们的研究结果表明，SPANXB1在嗜脑性乳腺癌细胞和脑转移样本中高度表达。功能分析显示，SPANXB1促进乳腺癌细胞侵袭、迁移、血管生成模拟（VM）形成和血脑屏障（BBB）外渗，从而加速脑转移过程。从机制上讲，SPANXB1通过组蛋白H3R17me2修饰促进MMP1启动子区域染色质打开，上调转录因子YY1，导致MMP1表达增加。体内实验进一步证实了SPANXB1在脑转移中的促进作用。值得注意的是，二甲双胍有效抑制了SPANXB1和MMP1的表达，从而减缓了BCBM的进展。本研究表明SPANXB1有潜力作为BCBM的诊断和治疗靶点。此外，我们的研究结果表明二甲双胍是一种很有希望的治疗这种高度侵袭性疾病的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

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.