• 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

三磷酸腺苷通过下调趋化因子受体4（CXCR4）和嘌呤能受体P2Y11抑制乳腺癌迁移和骨转移。

ATP Inhibits Breast Cancer Migration and Bone Metastasis through Down-Regulation of CXCR4 and Purinergic Receptor P2Y11.

作者信息

Liu Xiaowen, Riquelme Manuel A, Tian Yi, Zhao Dezhi, Acosta Francisca M, Gu Sumin, Jiang Jean X

机构信息

Department of Biochemistry and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.

Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China.

出版信息

Cancers (Basel). 2021 Aug 26;13(17):4293. doi: 10.3390/cancers13174293.

DOI:10.3390/cancers13174293
PMID:34503103
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8428338/
Abstract

ATP released by bone osteocytes is shown to activate purinergic signaling and inhibit the metastasis of breast cancer cells into the bone. However, the underlying molecular mechanism is not well understood. Here, we demonstrate the important roles of the CXCR4 and P2Y11 purinergic receptors in mediating the inhibitory effect of ATP on breast cancer cell migration and bone metastasis. Wound-healing and transwell migration assays showed that non-hydrolysable ATP analogue, ATPγS, inhibited migration of bone-tropic human breast cancer cells in a dose-dependent manner. BzATP, an agonist for P2X7 and an inducer for P2Y11 internalization, had a similar dose-dependent inhibition on cell migration. Both ATPγS and BzATP suppressed the expression of CXCR4, a chemokine receptor known to promote breast cancer bone metastasis, and knocking down CXCR4 expression by siRNA attenuated the inhibitory effect of ATPγS on cancer cell migration. While a P2X7 antagonist A804598 had no effect on the impact of ATPγS on cell migration, antagonizing P2Y11 by NF157 ablated the effect of ATPγS. Moreover, the reduction in P2Y11 expression by siRNA decreased cancer cell migration and abolished the impact of ATPγS on cell migration and CXCR4 expression. Similar to the effect of ATPγS on cell migration, antagonizing P2Y11 inhibited bone-tropic breast cancer cell migration in a dose-dependent manner. An in vivo study using an intratibial bone metastatic model showed that ATPγS inhibited breast cancer growth in the bone. Taken together, these results suggest that ATP inhibits bone-tropic breast cancer cells by down-regulating the P2Y11 purinergic receptor and the down-regulation of CXCR4 expression.

摘要

骨细胞释放的ATP可激活嘌呤能信号传导并抑制乳腺癌细胞向骨转移。然而，其潜在的分子机制尚未完全明确。在此，我们证明了CXCR4和P2Y11嘌呤能受体在介导ATP对乳腺癌细胞迁移和骨转移的抑制作用中发挥重要作用。伤口愈合和Transwell迁移实验表明，不可水解的ATP类似物ATPγS以剂量依赖性方式抑制亲骨性人乳腺癌细胞的迁移。BzATP是P2X7的激动剂和P2Y11内化的诱导剂，对细胞迁移具有类似的剂量依赖性抑制作用。ATPγS和BzATP均抑制CXCR4的表达，CXCR4是一种已知可促进乳腺癌骨转移的趋化因子受体，通过siRNA敲低CXCR4表达可减弱ATPγS对癌细胞迁移的抑制作用。虽然P2X7拮抗剂A804598对ATPγS对细胞迁移的影响没有作用，但用NF157拮抗P2Y11可消除ATPγS的作用。此外，通过siRNA降低P2Y11表达可减少癌细胞迁移，并消除ATPγS对细胞迁移和CXCR4表达的影响。与ATPγS对细胞迁移的作用类似，拮抗P2Y11以剂量依赖性方式抑制亲骨性乳腺癌细胞迁移。一项使用胫骨内骨转移模型的体内研究表明，ATPγS可抑制骨内乳腺癌的生长。综上所述，这些结果表明ATP通过下调P2Y11嘌呤能受体和CXCR4表达来抑制亲骨性乳腺癌细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/8f525bdaf605/cancers-13-04293-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/e7b4f7fd9e43/cancers-13-04293-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/9d1d6d9e97fe/cancers-13-04293-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/bd5f74081abc/cancers-13-04293-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/77b9a23b276e/cancers-13-04293-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/d97eb1b085b0/cancers-13-04293-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/7187a1af8d10/cancers-13-04293-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/8f525bdaf605/cancers-13-04293-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/e7b4f7fd9e43/cancers-13-04293-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/9d1d6d9e97fe/cancers-13-04293-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/bd5f74081abc/cancers-13-04293-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/77b9a23b276e/cancers-13-04293-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/d97eb1b085b0/cancers-13-04293-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/7187a1af8d10/cancers-13-04293-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9772/8428338/8f525bdaf605/cancers-13-04293-g007.jpg

相似文献

1
ATP Inhibits Breast Cancer Migration and Bone Metastasis through Down-Regulation of CXCR4 and Purinergic Receptor P2Y11.三磷酸腺苷通过下调趋化因子受体4（CXCR4）和嘌呤能受体P2Y11抑制乳腺癌迁移和骨转移。
Cancers (Basel). 2021 Aug 26;13(17):4293. doi: 10.3390/cancers13174293.
2
Differential impact of adenosine nucleotides released by osteocytes on breast cancer growth and bone metastasis.骨细胞释放的腺苷核苷酸对乳腺癌生长和骨转移的不同影响。
Oncogene. 2015 Apr 2;34(14):1831-42. doi: 10.1038/onc.2014.113. Epub 2014 May 19.
3
Carcinoma-specific expression of P2Y11 receptor and its contribution in ATP-induced purinergic signalling and cell migration in human hepatocellular carcinoma cells.P2Y11受体在人肝癌细胞中的癌特异性表达及其在ATP诱导的嘌呤能信号传导和细胞迁移中的作用
Oncotarget. 2017 Jun 6;8(23):37278-37290. doi: 10.18632/oncotarget.16191.
4
Crosstalk between purinergic receptor P2Y and chemokine receptor CXCR7 is regulated by CXCR4 in human macrophages.嘌呤能受体P2Y与趋化因子受体CXCR7之间的串扰由人类巨噬细胞中的CXCR4调控。
Cell Mol Life Sci. 2024 Mar 13;81(1):132. doi: 10.1007/s00018-024-05158-7.
5
Human P2Y Expression Level Affects Human P2X7 Receptor-Mediated Cell Death.人类P2Y表达水平影响人类P2X7受体介导的细胞死亡。
Front Immunol. 2018 Jun 8;9:1159. doi: 10.3389/fimmu.2018.01159. eCollection 2018.
6
Role of P2 Receptors as Modulators of Rat Eosinophil Recruitment in Allergic Inflammation.P2受体作为变应性炎症中大鼠嗜酸性粒细胞募集调节因子的作用
PLoS One. 2016 Jan 19;11(1):e0145392. doi: 10.1371/journal.pone.0145392. eCollection 2016.
7
Pharmacological characterization of the human P2Y11 receptor.人类P2Y11受体的药理学特性
Br J Pharmacol. 1999 Nov;128(6):1199-206. doi: 10.1038/sj.bjp.0702909.
8
Autocrine regulation of macrophage activation via exocytosis of ATP and activation of P2Y11 receptor.通过 ATP 的胞吐作用和 P2Y11 受体的激活实现巨噬细胞激活的自分泌调节。
PLoS One. 2013;8(4):e59778. doi: 10.1371/journal.pone.0059778. Epub 2013 Apr 5.
9
Thymoquinone Inhibits Bone Metastasis of Breast Cancer Cells Through Abrogation of the CXCR4 Signaling Axis.百里醌通过消除CXCR4信号轴抑制乳腺癌细胞的骨转移。
Front Pharmacol. 2018 Dec 4;9:1294. doi: 10.3389/fphar.2018.01294. eCollection 2018.
10
Alanine-(87)-threonine polymorphism impairs signaling and internalization of the human P2Y11 receptor, when co-expressed with the P2Y1 receptor.丙氨酰-（87）-苏氨酸多态性会损害人 P2Y11 受体与 P2Y1 受体共表达时的信号转导和内化。
J Neurochem. 2014 May;129(4):602-13. doi: 10.1111/jnc.12666. Epub 2014 Feb 13.

引用本文的文献

1
and colorectal cancer: A paradoxical role revealed through metabolite profiling and prognostic modeling.与结直肠癌：通过代谢物谱分析和预后模型揭示的矛盾作用。
World J Clin Oncol. 2025 Apr 24;16(4):104182. doi: 10.5306/wjco.v16.i4.104182.
2
The Use of Biologics for Targeting GPCRs in Metastatic Cancers.生物制剂在转移性癌症中靶向G蛋白偶联受体的应用
BioTech (Basel). 2025 Jan 30;14(1):7. doi: 10.3390/biotech14010007.
3
Connexin 43 hemichannels and related diseases.连接蛋白43半通道与相关疾病

本文引用的文献

1
The purinergic receptor P2Y11 choreographs the polarization, mitochondrial metabolism, and migration of T lymphocytes.嘌呤能受体 P2Y11 协调 T 淋巴细胞的极化、线粒体代谢和迁移。
Sci Signal. 2020 Sep 29;13(651):eaba3300. doi: 10.1126/scisignal.aba3300.
2
A Adenosine Receptor and Cancer.腺嘌呤受体与癌症。
Int J Mol Sci. 2019 Oct 17;20(20):5139. doi: 10.3390/ijms20205139.
3
Breast cancer statistics, 2019.乳腺癌统计数据，2019 年。
Antib Ther. 2024 Nov 11;7(4):361-369. doi: 10.1093/abt/tbae024. eCollection 2024 Oct.
4
Identification and validation of mRNA profiles linked to ATP- induced cell death represent a novel prognostic model for breast cancer.鉴定和验证与 ATP 诱导细胞死亡相关的 mRNA 谱代表了一种新的乳腺癌预后模型。
Front Immunol. 2024 Nov 1;15:1483498. doi: 10.3389/fimmu.2024.1483498. eCollection 2024.
5
Antibody-activation of connexin hemichannels in bone osteocytes with ATP release suppresses breast cancer and osteosarcoma malignancy.抗体激活骨细胞缝隙连接半通道伴 ATP 释放抑制乳腺癌和骨肉瘤恶性进展。
Cell Rep. 2024 Jul 23;43(7):114377. doi: 10.1016/j.celrep.2024.114377. Epub 2024 Jun 17.
6
Novel insights into osteocyte and inter-organ/tissue crosstalk.骨细胞与器官/组织间对话的新见解。
Front Endocrinol (Lausanne). 2024 Jan 17;14:1308408. doi: 10.3389/fendo.2023.1308408. eCollection 2023.
7
Primary mouse myoblast metabotropic purinoceptor profiles and calcium signalling differ with their muscle origin and are altered in mdx dystrophinopathy.原代鼠肌母细胞代谢型嘌呤能受体谱及其钙信号转导随其肌肉起源而不同，并在 mdx 肌营养不良症中发生改变。
Sci Rep. 2023 Jun 8;13(1):9333. doi: 10.1038/s41598-023-36545-y.
8
Ca-Activated K Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review.成体组织祖细胞中的钙激活钾通道：综述。
Int J Mol Sci. 2023 Apr 5;24(7):6796. doi: 10.3390/ijms24076796.
9
Purinergic signaling: Diverse effects and therapeutic potential in cancer.嘌呤能信号传导：在癌症中的多种作用及治疗潜力
Front Oncol. 2023 Jan 18;13:1058371. doi: 10.3389/fonc.2023.1058371. eCollection 2023.
10
P2X7 receptor involved in antitumor activity of atractylenolide I in human cervical cancer cells.P2X7 受体参与了白术内酯 I 对人宫颈癌的抗肿瘤作用。
Purinergic Signal. 2023 Mar;19(1):145-153. doi: 10.1007/s11302-022-09854-6. Epub 2022 Mar 2.
CA Cancer J Clin. 2019 Nov;69(6):438-451. doi: 10.3322/caac.21583. Epub 2019 Oct 2.
4
CXCR4 as a prognostic biomarker in gastrointestinal cancer: a meta-analysis.CXCR4 作为胃肠道癌症的预后生物标志物：一项荟萃分析。
Biomarkers. 2019 Sep;24(6):510-516. doi: 10.1080/1354750X.2019.1637941. Epub 2019 Jul 7.
5
Impact of CXCR4 and CXCR7 knockout by CRISPR/Cas9 on the function of triple-negative breast cancer cells.CRISPR/Cas9介导的CXCR4和CXCR7基因敲除对三阴性乳腺癌细胞功能的影响
Onco Targets Ther. 2019 May 17;12:3849-3858. doi: 10.2147/OTT.S195661. eCollection 2019.
6
Extracellular ATP and P2 purinergic signalling in the tumour microenvironment.细胞外 ATP 与肿瘤微环境中的 P2 嘌呤能信号转导。
Nat Rev Cancer. 2018 Oct;18(10):601-618. doi: 10.1038/s41568-018-0037-0.
7
Peptide density targets and impedes triple negative breast cancer metastasis.肽密度靶向并阻碍三阴性乳腺癌转移。
Nat Commun. 2018 Jul 4;9(1):2612. doi: 10.1038/s41467-018-05035-5.
8
Activating P2X7 Receptors Increases Proliferation of Human Pancreatic Cancer Cells via ERK1/2 and JNK.激活P2X7受体通过ERK1/2和JNK增加人胰腺癌细胞的增殖。
Pancreas. 2018 May/Jun;47(5):643-651. doi: 10.1097/MPA.0000000000001055.
9
Breast cancer metastasis to liver and lung is facilitated by Pit-1-CXCL12-CXCR4 axis.乳腺癌转移至肝和肺是由 Pit-1-CXCL12-CXCR4 轴促进的。
Oncogene. 2018 Mar;37(11):1430-1444. doi: 10.1038/s41388-017-0036-8. Epub 2018 Jan 11.
10
Evaluation of the Cell Invasion and Migration Process: A Comparison of the Video Microscope-based Scratch Wound Assay and the Boyden Chamber Assay.细胞侵袭和迁移过程的评估：基于视频显微镜的划痕试验与博伊登室试验的比较
J Vis Exp. 2017 Nov 17(129):56337. doi: 10.3791/56337.