• 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

Claudin-11通过激活MT1-MMP增强小细胞肺癌的侵袭和转移能力。

Claudin-11 Enhances Invasive and Metastatic Abilities of Small-Cell Lung Cancer Through MT1-MMP Activation.

作者信息

Sakamoto Shuichi, Inoue Hiroyuki, Takino Takahisa, Kohda Yasuko, Yoshida Junjiro, Ohba Shunichi, Usami Ihomi, Suzuki Takeshi, Kawada Manabu, Hatakeyama Masanori

机构信息

Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Numazu, Japan.

Institute of Liberal Arts & Science, Kanazawa University, Kanazawa, Ishikawa, Japan.

出版信息

Cancer Sci. 2025 Jun;116(6):1773-1784. doi: 10.1111/cas.70038. Epub 2025 Mar 13.

DOI:10.1111/cas.70038
PMID:40079504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12127104/
Abstract

Small-cell lung cancer (SCLC) is an aggressive tumor characterized by the frequent development of distant metastases. This study aimed to explore the mechanism of SCLC metastasis using an originally developed orthotopic transplantation model with DMS273 cells. An analysis of G3H cells, a highly metastatic subline of DMS273 cells, revealed that claudin-11 promotes the invasive and metastatic ability of the cells. Further analysis revealed that membrane type 1-matrix metalloproteinase (MT1-MMP), which degrades a wide range of extracellular matrix components, was coprecipitated with claudin-11. Gelatin zymography revealed that claudin-11 enhanced MT1-MMP activity, and MT1-MMP silencing suppressed the invasive and metastatic ability of G3H cells. Moreover, in MT1-MMP silencing DMS273 cells, the enhancement of invasion and metastatic potential induced by CLDN11 overexpression was abolished. These results demonstrate that claudin-11 enhances the invasive capacity of the cells by activating MT1-MMP, which promotes metastatic formation in the orthotopic transplantation model. Additionally, claudin-11 expression was detected in SCLC tumor samples, and higher expression of CLDN11 correlated with poor prognosis in patients with SCLC. These findings suggest that the claudin-11/MT1-MMP axis plays an important role in SCLC pathogenesis.

摘要

小细胞肺癌（SCLC）是一种侵袭性肿瘤，其特征是频繁发生远处转移。本研究旨在使用最初开发的DMS273细胞原位移植模型探索SCLC转移的机制。对DMS273细胞的高转移亚系G3H细胞进行分析，结果显示紧密连接蛋白-11（claudin-11）可促进细胞的侵袭和转移能力。进一步分析表明，能降解多种细胞外基质成分的膜型1-基质金属蛋白酶（MT1-MMP）与claudin-11共沉淀。明胶酶谱分析显示claudin-11增强了MT1-MMP的活性，而MT1-MMP沉默则抑制了G3H细胞的侵袭和转移能力。此外，在MT1-MMP沉默的DMS273细胞中，CLDN11过表达诱导的侵袭和转移潜能增强被消除。这些结果表明，claudin-11通过激活MT1-MMP增强细胞的侵袭能力，而MT1-MMP在原位移植模型中促进转移形成。此外，在SCLC肿瘤样本中检测到claudin-11表达，CLDN11的高表达与SCLC患者的不良预后相关。这些发现提示claudin-11/MT1-MMP轴在SCLC发病机制中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/251bd4f11082/CAS-116-1773-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/e95d17424a48/CAS-116-1773-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/6d607adf5085/CAS-116-1773-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/3a1756f2372b/CAS-116-1773-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/5d75621e4f8a/CAS-116-1773-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/a33171b510d3/CAS-116-1773-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/13fa950243b7/CAS-116-1773-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/e3bbe59d8eb9/CAS-116-1773-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/251bd4f11082/CAS-116-1773-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/e95d17424a48/CAS-116-1773-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/6d607adf5085/CAS-116-1773-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/3a1756f2372b/CAS-116-1773-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/5d75621e4f8a/CAS-116-1773-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/a33171b510d3/CAS-116-1773-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/13fa950243b7/CAS-116-1773-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/e3bbe59d8eb9/CAS-116-1773-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e6/12127104/251bd4f11082/CAS-116-1773-g006.jpg

相似文献

1
Claudin-11 Enhances Invasive and Metastatic Abilities of Small-Cell Lung Cancer Through MT1-MMP Activation.Claudin-11通过激活MT1-MMP增强小细胞肺癌的侵袭和转移能力。
Cancer Sci. 2025 Jun;116(6):1773-1784. doi: 10.1111/cas.70038. Epub 2025 Mar 13.
2
Interferon-Induced Transmembrane Protein 1 (IFITM1) Promotes Distant Metastasis of Small Cell Lung Cancer.干扰素诱导跨膜蛋白 1（IFITM1）促进小细胞肺癌的远处转移。
Int J Mol Sci. 2020 Jul 13;21(14):4934. doi: 10.3390/ijms21144934.
3
New metastatic model of human small-cell lung cancer by orthotopic transplantation in mice.通过小鼠原位移植建立人小细胞肺癌新的转移模型。
Cancer Sci. 2015 Apr;106(4):367-74. doi: 10.1111/cas.12624. Epub 2015 Feb 26.
4
Tight junction protein claudin-1 enhances the invasive activity of oral squamous cell carcinoma cells by promoting cleavage of laminin-5 gamma2 chain via matrix metalloproteinase (MMP)-2 and membrane-type MMP-1.紧密连接蛋白claudin-1通过基质金属蛋白酶（MMP）-2和膜型MMP-1促进层粘连蛋白-5γ2链的裂解，从而增强口腔鳞状细胞癌细胞的侵袭活性。
Cancer Res. 2006 May 15;66(10):5251-7. doi: 10.1158/0008-5472.CAN-05-4478.
5
The tetraspanin CD81 protein increases melanoma cell motility by up-regulating metalloproteinase MT1-MMP expression through the pro-oncogenic Akt-dependent Sp1 activation signaling pathways.四跨膜蛋白 CD81 通过激活 Akt 依赖性致癌信号通路 Sp1 上调金属蛋白酶 MT1-MMP 的表达从而增加黑色素瘤细胞的迁移能力。
J Biol Chem. 2014 May 30;289(22):15691-704. doi: 10.1074/jbc.M113.534206. Epub 2014 Apr 14.
6
SNX27-retromer assembly recycles MT1-MMP to invadopodia and promotes breast cancer metastasis.SNX27- 网格蛋白复体型回收 MT1-MMP 至入侵伪足，促进乳腺癌转移。
J Cell Biol. 2020 Jan 6;219(1). doi: 10.1083/jcb.201812098.
7
Enhanced membrane-type 1 matrix metalloproteinase expression by hyaluronan oligosaccharides in breast cancer cells facilitates CD44 cleavage and tumor cell migration.透明质酸寡糖通过增强乳腺癌细胞膜型 1 基质金属蛋白酶的表达促进 CD44 裂解和肿瘤细胞迁移。
Oncol Rep. 2012 Nov;28(5):1808-14. doi: 10.3892/or.2012.1993. Epub 2012 Aug 24.
8
Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis.肿瘤细胞 MT1-MMP 对于骨肉瘤肿瘤生长、骨质降解和肺转移是可有可无的。
Sci Rep. 2020 Nov 5;10(1):19138. doi: 10.1038/s41598-020-75995-6.
9
Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases.紧密连接蛋白促进膜型基质金属蛋白酶介导的前基质金属蛋白酶-2的激活。
J Biol Chem. 2001 Jul 27;276(30):28204-11. doi: 10.1074/jbc.M103083200. Epub 2001 May 29.
10
Cancer cell-associated MT1-MMP promotes blood vessel invasion and distant metastasis in triple-negative mammary tumors.肿瘤细胞相关的 MT1-MMP 促进三阴性乳腺肿瘤中的血管侵袭和远处转移。
Cancer Res. 2011 Jul 1;71(13):4527-38. doi: 10.1158/0008-5472.CAN-10-4376. Epub 2011 May 13.

本文引用的文献

1
Claudin-11 in health and disease: implications for myelin disorders, hearing, and fertility.紧密连接蛋白11在健康与疾病中的作用：对髓鞘疾病、听力及生育能力的影响
Front Cell Neurosci. 2024 Jan 17;17:1344090. doi: 10.3389/fncel.2023.1344090. eCollection 2023.
2
MT1-MMP as a Key Regulator of Metastasis.MT1-MMP 作为转移的关键调节因子。
Cells. 2023 Aug 31;12(17):2187. doi: 10.3390/cells12172187.
3
The role of claudins in homeostasis.紧密连接蛋白在稳态中的作用。
Nat Rev Nephrol. 2023 Sep;19(9):587-603. doi: 10.1038/s41581-023-00731-y. Epub 2023 Jun 21.
4
Proteolytic cleavage of membrane proteins by membrane type-1 MMP regulates cancer malignant progression.膜型基质金属蛋白酶对膜蛋白的蛋白水解切割调控着癌症的恶性进展。
Cancer Sci. 2023 Feb;114(2):348-356. doi: 10.1111/cas.15638. Epub 2022 Nov 24.
5
Context-Dependent Roles of Claudins in Tumorigenesis.紧密连接蛋白在肿瘤发生中的上下文依赖作用。
Front Oncol. 2021 Jul 20;11:676781. doi: 10.3389/fonc.2021.676781. eCollection 2021.
6
Mechanisms of small cell lung cancer metastasis.小细胞肺癌转移的机制。
EMBO Mol Med. 2021 Jan 11;13(1):e13122. doi: 10.15252/emmm.202013122. Epub 2020 Dec 9.
7
Interferon-Induced Transmembrane Protein 1 (IFITM1) Promotes Distant Metastasis of Small Cell Lung Cancer.干扰素诱导跨膜蛋白 1（IFITM1）促进小细胞肺癌的远处转移。
Int J Mol Sci. 2020 Jul 13;21(14):4934. doi: 10.3390/ijms21144934.
8
Identification of claudin-2, -6, -11 and -14 as prognostic markers in human breast carcinoma.鉴定紧密连接蛋白-2、-6、-11和-14作为人类乳腺癌的预后标志物。
Int J Clin Exp Pathol. 2019 Jun 1;12(6):2195-2204. eCollection 2019.
9
Snail-induced claudin-11 prompts collective migration for tumour progression.蜗牛诱导 Claudin-11 促使肿瘤进展的集体迁移。
Nat Cell Biol. 2019 Feb;21(2):251-262. doi: 10.1038/s41556-018-0268-z. Epub 2019 Jan 21.
10
Inactivation of the tight junction gene CLDN11 by aberrant hypermethylation modulates tubulins polymerization and promotes cell migration in nasopharyngeal carcinoma.异常超甲基化导致紧密连接基因 CLDN11 失活，调节微管聚合并促进鼻咽癌中的细胞迁移。
J Exp Clin Cancer Res. 2018 May 10;37(1):102. doi: 10.1186/s13046-018-0754-y.