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胶原蛋白Xα1(CoL10A1)通过上皮-间质转化(EMT)途径对乳腺癌颅内血管侵袭和细胞增殖的调节作用。

The regulatory effect of CoL10A1 to the intracranial vascular invasion and cell proliferation in breast cancer via EMT pathway.

作者信息

Wang Xiaoyin, Ma Shunchang, Li Shaomin, Jia Wang, Zhang Dainan

机构信息

Henan Key Laboratory of Neurorestoratology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China.

Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

出版信息

Sci Rep. 2025 Apr 1;15(1):11040. doi: 10.1038/s41598-025-87475-w.

DOI:10.1038/s41598-025-87475-w
PMID:40169690
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11962102/
Abstract

With advances in breast cancer (BC) treatment technology, although it could prolong the BC patients' survival, brain metastasis (BM) is increasing gradually. Patients with brain metastasis of breast cancer (BMBC) could have the decline of survival rate and quality of life. Investigate the regulatory role of Collagen Type X Alpha 1 Chain (CoL10A1) in BMBC process was the aim of this study. CoL10A1 expression was analyzed from TCGA database and clinical tissues, and then detected the regulation of CoL10A1 on BC cells proliferation, migration, and invasion in BC cell lines and mouse models. Our findings indicated that BMBC tissues have significant levels of CoL10A1 expression. BC cells proliferation, migration and invasion may be inhibited by knocking down Co10A1 in vitro and in vivo. In addition, we found that knocking down CoL10A1 could reduce the penetration of 468 cells into hCMEC/D3 cells. Knocking down CoL10A1 regulated the epithelial-mesenchymal transition (EMT) pathway related proteins expression. CoL10A1 could regulate BC cells proliferation, migration and invasion, affect the penetration into hCMEC/D3 cells in vitro, and inhibit the intracranial vascular invasion in mouse models. These results suggested that CoL10A1 may be a new target for treating human BMBC.

摘要

随着乳腺癌(BC)治疗技术的进步,尽管其可延长BC患者的生存期,但脑转移(BM)却在逐渐增加。乳腺癌脑转移(BMBC)患者的生存率和生活质量会下降。本研究旨在探讨Ⅹ型胶原蛋白α1链(CoL10A1)在BMBC过程中的调控作用。从TCGA数据库和临床组织中分析CoL10A1的表达,然后在BC细胞系和小鼠模型中检测CoL10A1对BC细胞增殖、迁移和侵袭的调控作用。我们的研究结果表明,BMBC组织中CoL10A1表达水平显著。在体外和体内敲低Co10A1可能会抑制BC细胞的增殖、迁移和侵袭。此外,我们发现敲低CoL10A1可减少468细胞对hCMEC/D3细胞的穿透。敲低CoL10A1可调节上皮-间质转化(EMT)途径相关蛋白的表达。CoL10A1可调节BC细胞的增殖、迁移和侵袭,影响体外对hCMEC/D3细胞的穿透,并抑制小鼠模型中的颅内血管侵袭。这些结果表明,CoL10A1可能是治疗人类BMBC的一个新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11962102/16941ff079e5/41598_2025_87475_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11962102/c8d674ff128e/41598_2025_87475_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11962102/f595ec43098c/41598_2025_87475_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11962102/7a402ae50214/41598_2025_87475_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11962102/16941ff079e5/41598_2025_87475_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11962102/c8d674ff128e/41598_2025_87475_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11962102/10f4742a9ce1/41598_2025_87475_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11962102/60dae6f065a6/41598_2025_87475_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11962102/bf160ab26ce6/41598_2025_87475_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11962102/f595ec43098c/41598_2025_87475_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11962102/7a402ae50214/41598_2025_87475_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11962102/16941ff079e5/41598_2025_87475_Fig8_HTML.jpg

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本文引用的文献

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Targeting the epithelial-mesenchymal transition (EMT) pathway with combination of Wnt inhibitor and chalcone complexes in lung cancer cells.靶向肺癌细胞上皮-间充质转化(EMT)通路的 Wnt 抑制剂与查尔酮复合物的联合应用。
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High expression COL10A1 promotes breast cancer progression and predicts poor prognosis.高表达的COL10A1促进乳腺癌进展并预示不良预后。
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COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma.COL10A1可对结肠癌的侵袭性进行分层,并与肿瘤实质中的细胞外基质和免疫细胞富集相关联。
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High COL10A1 expression potentially contributes to poor outcomes in gastric cancer with the help of LEF1 and Wnt2.COL10A1 高表达可能有助于 LEF1 和 Wnt2 协助下的胃癌不良预后。
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