• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

弗林蛋白酶抑制剂通过Wnt信号通路下调MT1-MMP的表达水平，从而下调骨肉瘤细胞的迁移能力。

A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway.

作者信息

Liu Bingshan, Li Guojun, Wang Xiao, Liu Yang

机构信息

Department of Orthopaedics, Huaihe Hospital, Henan University, Kaifeng, Henan 475001, P.R. China.

出版信息

Oncol Lett. 2014 Apr;7(4):1033-1038. doi: 10.3892/ol.2014.1839. Epub 2014 Jan 29.

DOI:10.3892/ol.2014.1839
PMID:24944664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3961323/
Abstract

This study aimed to explore the exact mechanism of the effect of a furin inhibitor on the migration and invasion of MG-63 and Saos-2 osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were treated with regular culture medium in the presence or absence of 480 nM α1-antitrypsin Portland (α1-PDX). Wound-healing and Transwell assays were used for the detection of the effects of α1-PDX on MG-63 and Saos-2 osteosarcoma cell migration and invasion. Western blot analysis and reverse transcription-polymerase chain reaction were performed to detect the expression levels of membrane type I matrix metalloproteinase (MT1-MMP), Wnt and β-catenin. A chromatin immunoprecipitation assay was used for detection of the levels of MT1-MMP gene transcription activity. The results showed that α1-PDX treatment significantly reduced the migration and invasion ability of the cells. Notably, the expression levels of MT1-MMP decreased evidently upon α1-PDX treatment, paralleled with reductions in the expression levels of Wnt and β-catenin. Further analysis of the transcriptional activity of MT1-MMP revealed that the α1-PDX-induced downregulation of the levels of MT1-MMP was mediated by the Wnt signaling pathway. These data suggest that α1-PDX plays a vital role in inhibiting MG-63 and Saos-2 osteosarcoma cell migration and invasion by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway.

摘要

本研究旨在探究弗林蛋白酶抑制剂对MG-63和Saos-2骨肉瘤细胞迁移和侵袭影响的具体机制。在存在或不存在480 nM α1-抗胰蛋白酶波特兰（α1-PDX）的情况下，用常规培养基处理MG-63和Saos-2骨肉瘤细胞。采用伤口愈合实验和Transwell实验检测α1-PDX对MG-63和Saos-2骨肉瘤细胞迁移和侵袭的影响。进行蛋白质免疫印迹分析和逆转录-聚合酶链反应以检测膜型I基质金属蛋白酶（MT1-MMP）、Wnt和β-连环蛋白的表达水平。采用染色质免疫沉淀实验检测MT1-MMP基因转录活性水平。结果显示，α1-PDX处理显著降低了细胞的迁移和侵袭能力。值得注意的是，α1-PDX处理后MT1-MMP的表达水平明显下降，同时Wnt和β-连环蛋白的表达水平也降低。对MT1-MMP转录活性的进一步分析表明，α1-PDX诱导的MT1-MMP水平下调是由Wnt信号通路介导的。这些数据表明，α1-PDX通过Wnt信号通路下调MT1-MMP的表达水平，在抑制MG-63和Saos-2骨肉瘤细胞迁移和侵袭中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa1b/3961323/8ac2d37c0843/OL-07-04-1033-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa1b/3961323/bb3dc0238a7b/OL-07-04-1033-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa1b/3961323/5f94bcc25eed/OL-07-04-1033-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa1b/3961323/53675ba71f77/OL-07-04-1033-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa1b/3961323/e3c53948c147/OL-07-04-1033-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa1b/3961323/8ac2d37c0843/OL-07-04-1033-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa1b/3961323/bb3dc0238a7b/OL-07-04-1033-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa1b/3961323/5f94bcc25eed/OL-07-04-1033-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa1b/3961323/53675ba71f77/OL-07-04-1033-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa1b/3961323/e3c53948c147/OL-07-04-1033-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa1b/3961323/8ac2d37c0843/OL-07-04-1033-g04.jpg

相似文献

1
A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway.弗林蛋白酶抑制剂通过Wnt信号通路下调MT1-MMP的表达水平，从而下调骨肉瘤细胞的迁移能力。
Oncol Lett. 2014 Apr;7(4):1033-1038. doi: 10.3892/ol.2014.1839. Epub 2014 Jan 29.
2
Effect of Matrine on HPAC cell migration by down-regulating the expression of MT1-MMP via Wnt signaling.苦参碱通过 Wnt 信号下调 MT1-MMP 的表达抑制 HPAC 细胞迁移。
Cancer Cell Int. 2015 Jun 11;15:59. doi: 10.1186/s12935-015-0210-4. eCollection 2015.
3
Stable expression of α1-antitrypsin Portland in MDA-MB-231 cells increased MT1-MMP and MMP-9 levels, but reduced tumour progression.α1-抗胰蛋白酶波特兰在MDA-MB-231细胞中的稳定表达增加了MT1-MMP和MMP-9的水平，但降低了肿瘤进展。
J Cell Commun Signal. 2018 Jun;12(2):479-488. doi: 10.1007/s12079-017-0407-5. Epub 2017 Aug 29.
4
[Effects of α1-PDX, a furin inhibitor, on growth, invasion, and tumorigenicity of cervical cancer HeLa cells].弗林蛋白酶抑制剂α1-PDX对宫颈癌HeLa细胞生长、侵袭及致瘤性的影响
Nan Fang Yi Ke Da Xue Xue Bao. 2015 Mar;35(3):432-6.
5
Exerts an Anticancer Effect on Human Osteosarcoma Cells via Suppressing the Wnt/β-Catenin Signaling Pathway.通过抑制 Wnt/β-连环蛋白信号通路对人骨肉瘤细胞发挥抗癌作用。
Integr Cancer Ther. 2019 Jan-Dec;18:1534735419890917. doi: 10.1177/1534735419890917.
6
Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing Wnt/β-catenin signaling pathway.夹竹桃苷通过抑制Wnt/β-连环蛋白信号通路对骨肉瘤细胞的体外增殖、迁移和侵袭的抑制作用
J Exp Clin Cancer Res. 2015 Oct 6;34:115. doi: 10.1186/s13046-015-0232-8.
7
Effects of SOST Gene Silencing on Proliferation, Apoptosis, Invasion, and Migration of Human Osteosarcoma Cells Through the Wnt/β-Catenin Signaling Pathway.SOST基因沉默通过Wnt/β-连环蛋白信号通路对人骨肉瘤细胞增殖、凋亡、侵袭及迁移的影响
Calcif Tissue Int. 2017 Jun;100(6):551-564. doi: 10.1007/s00223-016-0231-6. Epub 2017 Feb 28.
8
Activation-coupled membrane-type 1 matrix metalloproteinase membrane trafficking.激活偶联的膜型1基质金属蛋白酶膜转运
Biochem J. 2007 Oct 15;407(2):171-7. doi: 10.1042/BJ20070552.
9
Involvement of furin-like proprotein convertases in the arterial response to injury.弗林样前蛋白转化酶在动脉损伤反应中的作用。
Cardiovasc Res. 2005 Oct 1;68(1):136-43. doi: 10.1016/j.cardiores.2005.05.016.
10
Melittin inhibits lung metastasis of human osteosarcoma: Evidence of wnt/β-catenin signaling pathway participation.蜂毒素抑制人骨肉瘤肺转移：Wnt/β-连环蛋白信号通路参与的证据。
Toxicon. 2021 Jul 30;198:132-142. doi: 10.1016/j.toxicon.2021.04.024. Epub 2021 Apr 28.

引用本文的文献

1
Comparison of Selected Non-Coding RNAs and Gene Expression Profiles between Common Osteosarcoma Cell Lines.常见骨肉瘤细胞系中选定非编码RNA与基因表达谱的比较
Cancers (Basel). 2022 Sep 19;14(18):4533. doi: 10.3390/cancers14184533.
2
The effect of baicalein on Wnt/β-catenin pathway and miR-25 expression in Saos-2 osteosarcoma cell line.黄芩素对 Saos-2 骨肉瘤细胞系中 Wnt/β-catenin 通路和 miR-25 表达的影响。
Turk J Med Sci. 2020 Jun 23;50(44):1168-1179. doi: 10.3906/sag-2001-161.
3
MMP14 in Sarcoma: A Regulator of Tumor Microenvironment Communication in Connective Tissues.

本文引用的文献

1
Three-dimensional collagen I promotes gemcitabine resistance in pancreatic cancer through MT1-MMP-mediated expression of HMGA2.三维胶原 I 通过 MT1-MMP 介导的 HMGA2 表达促进胰腺癌对吉西他滨的耐药性。
Cancer Res. 2011 Feb 1;71(3):1019-28. doi: 10.1158/0008-5472.CAN-10-1855. Epub 2010 Dec 8.
2
Matrix metalloproteinases: regulators of the tumor microenvironment.基质金属蛋白酶：肿瘤微环境的调节剂。
Cell. 2010 Apr 2;141(1):52-67. doi: 10.1016/j.cell.2010.03.015.
3
Wnt/Planar cell polarity signaling: a new paradigm for cancer therapy.
基质金属蛋白酶 14 在肉瘤中的作用：结缔组织中肿瘤微环境通讯的调节因子。
Cells. 2019 Aug 28;8(9):991. doi: 10.3390/cells8090991.
4
New Insights about the Wnt/β-Catenin Signaling Pathway in Primary Bone Tumors and Their Microenvironment: A Promising Target to Develop Therapeutic Strategies?原发性骨肿瘤及其微环境中 Wnt/β-连环蛋白信号通路的新见解：开发治疗策略的有前途靶点？
Int J Mol Sci. 2019 Jul 31;20(15):3751. doi: 10.3390/ijms20153751.
5
Stable expression of α1-antitrypsin Portland in MDA-MB-231 cells increased MT1-MMP and MMP-9 levels, but reduced tumour progression.α1-抗胰蛋白酶波特兰在MDA-MB-231细胞中的稳定表达增加了MT1-MMP和MMP-9的水平，但降低了肿瘤进展。
J Cell Commun Signal. 2018 Jun;12(2):479-488. doi: 10.1007/s12079-017-0407-5. Epub 2017 Aug 29.
6
Lipid raft localization of epidermal growth factor receptor alters matrix metalloproteinase-1 expression in SiHa cells via the MAPK/ERK signaling pathway.表皮生长因子受体的脂筏定位通过MAPK/ERK信号通路改变SiHa细胞中基质金属蛋白酶-1的表达。
Oncol Lett. 2016 Dec;12(6):4991-4998. doi: 10.3892/ol.2016.5307. Epub 2016 Oct 24.
7
The Proprotein Convertase Furin Contributes to Rhabdomyosarcoma Malignancy by Promoting Vascularization, Migration and Invasion.前蛋白转化酶弗林蛋白酶通过促进血管生成、迁移和侵袭促进横纹肌肉瘤的恶性发展。
PLoS One. 2016 Aug 22;11(8):e0161396. doi: 10.1371/journal.pone.0161396. eCollection 2016.
8
Glycoprotein non-metastaticmelanoma protein B promotes glioma motility and angiogenesis through the Wnt/β-catenin signaling pathway.糖蛋白非转移性黑色素瘤蛋白B通过Wnt/β-连环蛋白信号通路促进胶质瘤的迁移和血管生成。
Exp Biol Med (Maywood). 2016 Nov;241(17):1968-1976. doi: 10.1177/1535370216654224. Epub 2016 Jun 21.
9
Matrix metalloproteinase 14 modulates signal transduction and angiogenesis in the cornea.基质金属蛋白酶14调节角膜中的信号转导和血管生成。
Surv Ophthalmol. 2016 Jul-Aug;61(4):478-97. doi: 10.1016/j.survophthal.2015.11.006. Epub 2015 Dec 2.
10
Bone Sarcomas in Pediatrics: Progress in Our Understanding of Tumor Biology and Implications for Therapy.儿科骨肉瘤：我们对肿瘤生物学的理解进展及其对治疗的意义
Paediatr Drugs. 2015 Aug;17(4):257-71. doi: 10.1007/s40272-015-0134-4.
Wnt/平面细胞极性信号通路：癌症治疗的新范例。
Mol Cancer Ther. 2009 Aug;8(8):2103-9. doi: 10.1158/1535-7163.MCT-09-0282. Epub 2009 Aug 11.
4
Autocatalytic activation of the furin zymogen requires removal of the emerging enzyme's N-terminus from the active site.弗林蛋白酶原的自催化激活需要将新出现的酶的N端从活性位点去除。
PLoS One. 2009;4(4):e5031. doi: 10.1371/journal.pone.0005031. Epub 2009 Apr 7.
5
Role of furin in granular acidification in the endocrine pancreas: identification of the V-ATPase subunit Ac45 as a candidate substrate.弗林蛋白酶在内分泌胰腺颗粒酸化中的作用：鉴定V-ATP酶亚基Ac45为候选底物。
Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12319-24. doi: 10.1073/pnas.0800340105. Epub 2008 Aug 19.
6
The many ways of Wnt in cancer.Wnt在癌症中的多种作用方式。
Curr Opin Genet Dev. 2007 Feb;17(1):45-51. doi: 10.1016/j.gde.2006.12.007.
7
Structure and function of matrix metalloproteinases and TIMPs.基质金属蛋白酶和金属蛋白酶组织抑制因子的结构与功能
Cardiovasc Res. 2006 Feb 15;69(3):562-73. doi: 10.1016/j.cardiores.2005.12.002. Epub 2006 Jan 5.
8
WNT/PCP signaling pathway and human cancer (review).WNT/平面细胞极性信号通路与人类癌症（综述）
Oncol Rep. 2005 Dec;14(6):1583-8.
9
MT1-MMP: a potent modifier of pericellular microenvironment.基质金属蛋白酶-1：细胞周围微环境的强效调节剂。
J Cell Physiol. 2006 Jan;206(1):1-8. doi: 10.1002/jcp.20431.
10
Human carcinoma cell growth and invasiveness is impaired by the propeptide of the ubiquitous proprotein convertase furin.遍在的前蛋白转化酶弗林蛋白酶原肽可损害人癌细胞的生长和侵袭能力。
Cancer Res. 2005 May 15;65(10):4162-71. doi: 10.1158/0008-5472.CAN-04-2820.