• 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

WWP1通过靶向PTEN进行多聚泛素化修饰以促进腔面型乳腺癌的骨转移。

WWP1 targeting PTEN for polyubiquitination to promote bone metastasis of luminal breast cancer.

作者信息

Jiang Hao, Li Zhenxi, Xu Wei, Xiao Jianru

机构信息

Spine Tumor Center, Changzheng Hospital, Naval Medical University, 415 Feng Yang Road, Shanghai, 200003, People's Republic of China.

出版信息

Sci Rep. 2024 Dec 2;14(1):29950. doi: 10.1038/s41598-024-81541-5.

DOI:10.1038/s41598-024-81541-5
PMID:39622957
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11612161/
Abstract

Luminal breast cancer exhibits a high incidence of bone recurrence when metastasizing to distant organs. The mechanisms underlying the organotropism of luminal breast cancer cells remain unclear. In this study, we aimed to determine the role of WWP1 (WW domain-containing E3 ubiquitin protein ligase 1)-PTEN (phosphatase and tensin homolog deleted on chromosome ten) interaction in bone tropism in luminal breast cancer. We observed that WWP1 was overexpressed in luminal breast cancer tissues and associated with poor prognosis in breast cancer patients. In luminal breast cancer cells, WWP1 was found to mediate PTEN ubiquitination, resulting in the functional loss of PTEN. As a result, we demonstrate that WWP1 contributes to bone tropism in luminal breast cancer cells via the polyubiquitination of PTEN. Consequently, WWP1-mediated PTEN polyubiquitination contributed to the early metastasis of luminal breast cancer cells to the bone. Thus, our study provides a mechanistic insight into the bone tropism of luminal breast cancer cells and proposes a potential therapeutic strategy for mitigating cancer metastasis to the bone.

摘要

管腔型乳腺癌转移至远处器官时骨转移发生率较高。管腔型乳腺癌细胞器官趋向性的潜在机制尚不清楚。在本研究中，我们旨在确定WWP1（含WW结构域的E3泛素蛋白连接酶1）-PTEN（第10号染色体缺失的磷酸酶和张力蛋白同源物）相互作用在管腔型乳腺癌骨趋向性中的作用。我们观察到WWP1在管腔型乳腺癌组织中过表达，且与乳腺癌患者的不良预后相关。在管腔型乳腺癌细胞中，发现WWP1介导PTEN泛素化，导致PTEN功能丧失。因此，我们证明WWP1通过PTEN的多聚泛素化促进管腔型乳腺癌细胞的骨趋向性。因此，WWP1介导的PTEN多聚泛素化促进了管腔型乳腺癌细胞早期骨转移。因此，我们的研究为管腔型乳腺癌细胞的骨趋向性提供了机制性见解，并提出了减轻癌症骨转移的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/081f084659ef/41598_2024_81541_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/268b94e843e1/41598_2024_81541_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/7b75af9825b2/41598_2024_81541_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/3701c6662312/41598_2024_81541_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/da9f975b48b3/41598_2024_81541_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/ae2835960eb0/41598_2024_81541_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/081f084659ef/41598_2024_81541_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/268b94e843e1/41598_2024_81541_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/7b75af9825b2/41598_2024_81541_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/3701c6662312/41598_2024_81541_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/da9f975b48b3/41598_2024_81541_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/ae2835960eb0/41598_2024_81541_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d7/11612161/081f084659ef/41598_2024_81541_Fig6_HTML.jpg

相似文献

1
WWP1 targeting PTEN for polyubiquitination to promote bone metastasis of luminal breast cancer.WWP1通过靶向PTEN进行多聚泛素化修饰以促进腔面型乳腺癌的骨转移。
Sci Rep. 2024 Dec 2;14(1):29950. doi: 10.1038/s41598-024-81541-5.
2
WWP1 inhibition suppresses the proliferation of pancreatic cancer cells by regulating the PI3K-AKT pathway.WWP1抑制通过调节PI3K-AKT途径抑制胰腺癌细胞的增殖。
J Gastroenterol. 2025 Mar;60(3):370-384. doi: 10.1007/s00535-024-02192-x. Epub 2024 Dec 10.
3
Ubiquitin Ligase Activities of WWP1 Germline Variants K740N and N745S.WWP1 胚系变异 K740N 和 N745S 的泛素连接酶活性。
Biochemistry. 2021 Feb 9;60(5):357-364. doi: 10.1021/acs.biochem.0c00869. Epub 2021 Jan 20.
4
CYYR1 promotes the degradation of the E3 ubiquitin ligase WWP1 and is associated with favorable prognosis in breast cancer.CYYR1 促进 E3 泛素连接酶 WWP1 的降解，与乳腺癌的良好预后相关。
J Biol Chem. 2024 Sep;300(9):107601. doi: 10.1016/j.jbc.2024.107601. Epub 2024 Jul 24.
5
The ubiquitin E3 ligase WWP1 decreases CXCL12-mediated MDA231 breast cancer cell migration and bone metastasis.泛素 E3 连接酶 WWP1 降低了 CXCL12 介导的 MDA231 乳腺癌细胞迁移和骨转移。
Bone. 2012 Apr;50(4):813-23. doi: 10.1016/j.bone.2011.12.022. Epub 2012 Jan 11.
6
Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway.通过抑制 MYC-WWP1 抑制途径来激活 PTEN 肿瘤抑制因子以进行癌症治疗。
Science. 2019 May 17;364(6441). doi: 10.1126/science.aau0159.
7
Rak functions as a tumor suppressor by regulating PTEN protein stability and function.Rak通过调节PTEN蛋白的稳定性和功能发挥肿瘤抑制作用。
Cancer Cell. 2009 Apr 7;15(4):304-14. doi: 10.1016/j.ccr.2009.02.012.
8
The WWP1 ubiquitin E3 ligase increases TRAIL resistance in breast cancer.WWP1 泛素 E3 连接酶增加乳腺癌对 TRAIL 的耐药性。
Int J Cancer. 2012 Apr 1;130(7):1504-10. doi: 10.1002/ijc.26122. Epub 2011 May 30.
9
WWP1 Gain-of-Function Inactivation of PTEN in Cancer Predisposition.WWP1 功能获得性失活导致癌症易感性的 PTEN。
N Engl J Med. 2020 May 28;382(22):2103-2116. doi: 10.1056/NEJMoa1914919.
10
The WW domain containing E3 ubiquitin protein ligase 1 upregulates ErbB2 and EGFR through RING finger protein 11.含WW结构域的E3泛素蛋白连接酶1通过环指蛋白11上调ErbB2和表皮生长因子受体。
Oncogene. 2008 Nov 20;27(54):6845-55. doi: 10.1038/onc.2008.288. Epub 2008 Aug 25.

引用本文的文献

1
[WW domain-containing ubiquitin E3 ligase 1 regulates immune infiltration in tumor microenvironment of ovarian cancer].含WW结构域的泛素E3连接酶1调节卵巢癌肿瘤微环境中的免疫浸润
Nan Fang Yi Ke Da Xue Xue Bao. 2025 May 20;45(5):1063-1073. doi: 10.12122/j.issn.1673-4254.2025.05.20.

本文引用的文献

1
WWP1 E3 ligase at the crossroads of health and disease.WWP1 E3 连接酶处于健康与疾病的十字路口。
Cell Death Dis. 2023 Dec 21;14(12):853. doi: 10.1038/s41419-023-06380-0.
2
Deciphering breast cancer: from biology to the clinic.解读乳腺癌：从生物学到临床
Cell. 2023 Apr 13;186(8):1708-1728. doi: 10.1016/j.cell.2023.01.040. Epub 2023 Mar 16.
3
Semisynthetic Approach to the Analysis of Tumor Suppressor PTEN Ubiquitination.半合成方法分析肿瘤抑制因子 PTEN 的泛素化。
J Am Chem Soc. 2023 Mar 22;145(11):6039-6044. doi: 10.1021/jacs.2c13871. Epub 2023 Mar 10.
4
Clinical implications of the intrinsic molecular subtypes in hormone receptor-positive and HER2-negative metastatic breast cancer.激素受体阳性且人表皮生长因子受体2阴性转移性乳腺癌中内在分子亚型的临床意义
Cancer Treat Rev. 2023 Jan;112:102496. doi: 10.1016/j.ctrv.2022.102496. Epub 2022 Dec 9.
5
Bone Metastasis Initiation Is Coupled with Bone Remodeling through Osteogenic Differentiation of NG2+ Cells.骨转移起始通过 NG2+ 细胞的成骨分化与骨重塑相关联。
Cancer Discov. 2023 Feb 6;13(2):474-495. doi: 10.1158/2159-8290.CD-22-0220.
6
Linear ubiquitination of PTEN impairs its function to promote prostate cancer progression.PTEN 的线性泛素化使其功能受损，从而促进前列腺癌的进展。
Oncogene. 2022 Oct;41(44):4877-4892. doi: 10.1038/s41388-022-02485-6. Epub 2022 Oct 3.
7
PTEN Dual Lipid- and Protein-Phosphatase Function in Tumor Progression.PTEN在肿瘤进展中的双脂质和蛋白质磷酸酶功能
Cancers (Basel). 2022 Jul 28;14(15):3666. doi: 10.3390/cancers14153666.
8
Ubiquitin ligases: guardians of mammalian development.泛素连接酶：哺乳动物发育的守护者。
Nat Rev Mol Cell Biol. 2022 May;23(5):350-367. doi: 10.1038/s41580-021-00448-5. Epub 2022 Jan 25.
9
WWP1 inactivation enhances efficacy of PI3K inhibitors while suppressing their toxicities in breast cancer models.WWP1 失活增强了 PI3K 抑制剂在乳腺癌模型中的疗效，同时降低了它们的毒性。
J Clin Invest. 2021 Dec 15;131(24). doi: 10.1172/JCI140436.
10
Human prostate cancer bone metastases have an actionable immunosuppressive microenvironment.人前列腺癌骨转移具有可操作的免疫抑制微环境。
Cancer Cell. 2021 Nov 8;39(11):1464-1478.e8. doi: 10.1016/j.ccell.2021.09.005. Epub 2021 Oct 15.