• 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

层粘连蛋白是 B16 黑色素瘤细胞的趋化抑制剂：通过升高 cAMP 的 LPA5 受体发挥作用。

LPA is a chemorepellent for B16 melanoma cells: action through the cAMP-elevating LPA5 receptor.

机构信息

Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

出版信息

PLoS One. 2011;6(12):e29260. doi: 10.1371/journal.pone.0029260. Epub 2011 Dec 14.

DOI:10.1371/journal.pone.0029260
PMID:22195035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3237609/
Abstract

Lysophosphatidic acid (LPA), a lipid mediator enriched in serum, stimulates cell migration, proliferation and other functions in many cell types. LPA acts on six known G protein-coupled receptors, termed LPA(1-6), showing both overlapping and distinct signaling properties. Here we show that, unexpectedly, LPA and serum almost completely inhibit the transwell migration of B16 melanoma cells, with alkyl-LPA(18:1) being 10-fold more potent than acyl-LPA(18:1). The anti-migratory response to LPA is highly polarized and dependent on protein kinase A (PKA) but not Rho kinase activity; it is associated with a rapid increase in intracellular cAMP levels and PIP3 depletion from the plasma membrane. B16 cells express LPA(2), LPA(5) and LPA(6) receptors. We show that LPA-induced chemorepulsion is mediated specifically by the alkyl-LPA-preferring LPA(5) receptor (GPR92), which raises intracellular cAMP via a noncanonical pathway. Our results define LPA(5) as an anti-migratory receptor and they implicate the cAMP-PKA pathway, along with reduced PIP3 signaling, as an effector of chemorepulsion in B16 melanoma cells.

摘要

溶血磷脂酸（LPA）是一种富含于血清中的脂质介质，可刺激许多细胞类型的细胞迁移、增殖和其他功能。LPA 作用于六种已知的 G 蛋白偶联受体，称为 LPA（1-6），表现出重叠和独特的信号特性。在这里，我们出人意料地发现，LPA 和血清几乎完全抑制 B16 黑色素瘤细胞的 Transwell 迁移，其中烷基-LPA（18:1）的效力比酰基-LPA（18:1）强 10 倍。对 LPA 的抗迁移反应具有高度极化性，依赖于蛋白激酶 A（PKA）但不依赖于 Rho 激酶活性；它与细胞内 cAMP 水平的快速增加和质膜中 PIP3 的耗竭有关。B16 细胞表达 LPA（2）、LPA（5）和 LPA（6）受体。我们表明，LPA 诱导的趋化排斥作用是由烷基-LPA 优先 LPA（5）受体（GPR92）特异性介导的，该受体通过非典型途径增加细胞内 cAMP。我们的结果将 LPA（5）定义为抗迁移受体，并暗示 cAMP-PKA 途径以及减少的 PIP3 信号传导作为 B16 黑色素瘤细胞趋化排斥的效应子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/9982d2bdd0bd/pone.0029260.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/dc741f492622/pone.0029260.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/6cfba3a79054/pone.0029260.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/49928db9e7f0/pone.0029260.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/6970a266e78b/pone.0029260.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/46ee55129f61/pone.0029260.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/413a9e383df8/pone.0029260.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/b11ba00dce11/pone.0029260.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/9982d2bdd0bd/pone.0029260.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/dc741f492622/pone.0029260.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/6cfba3a79054/pone.0029260.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/49928db9e7f0/pone.0029260.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/6970a266e78b/pone.0029260.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/46ee55129f61/pone.0029260.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/413a9e383df8/pone.0029260.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/b11ba00dce11/pone.0029260.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2589/3237609/9982d2bdd0bd/pone.0029260.g008.jpg

相似文献

1
LPA is a chemorepellent for B16 melanoma cells: action through the cAMP-elevating LPA5 receptor.层粘连蛋白是 B16 黑色素瘤细胞的趋化抑制剂：通过升高 cAMP 的 LPA5 受体发挥作用。
PLoS One. 2011;6(12):e29260. doi: 10.1371/journal.pone.0029260. Epub 2011 Dec 14.
2
Protein kinase A inhibits lysophosphatidic acid induction of serum response factor via alterations in the actin cytoskeleton.蛋白激酶A通过改变肌动蛋白细胞骨架来抑制溶血磷脂酸诱导的血清反应因子。
Cell Signal. 2004 Oct;16(10):1141-51. doi: 10.1016/j.cellsig.2004.03.006.
3
GPR92 as a new G12/13- and Gq-coupled lysophosphatidic acid receptor that increases cAMP, LPA5.GPR92作为一种新的与G12/13和Gq偶联的溶血磷脂酸受体，即LPA5，可增加环磷酸腺苷（cAMP）。
J Biol Chem. 2006 Aug 18;281(33):23589-97. doi: 10.1074/jbc.M603670200. Epub 2006 Jun 14.
4
Linking αMSH with PPARγ in B16-F10 melanoma.将 αMSH 与 B16-F10 黑素瘤中的 PPARγ 连接。
Pigment Cell Melanoma Res. 2013 Jan;26(1):113-27. doi: 10.1111/j.1755-148X.2012.01042.x. Epub 2012 Sep 12.
5
Protein kinase A inhibits lysophosphatidic acid-induced migration of airway smooth muscle cells.蛋白激酶A抑制溶血磷脂酸诱导的气道平滑肌细胞迁移。
J Pharmacol Exp Ther. 2007 Jun;321(3):1102-8. doi: 10.1124/jpet.106.118042. Epub 2007 Mar 8.
6
LPA(4)/GPR23 is a lysophosphatidic acid (LPA) receptor utilizing G(s)-, G(q)/G(i)-mediated calcium signaling and G(12/13)-mediated Rho activation.溶血磷脂酸受体4（LPA(4)/GPR23）是一种利用G(s)、G(q)/G(i)介导的钙信号传导以及G(12/13)介导的Rho激活的溶血磷脂酸（LPA）受体。
J Biol Chem. 2007 Feb 16;282(7):4310-4317. doi: 10.1074/jbc.M610826200. Epub 2006 Dec 13.
7
Vascular smooth muscle migration and proliferation in response to lysophosphatidic acid (LPA) is mediated by LPA receptors coupling to Gq.溶血磷脂酸（LPA）诱导的血管平滑肌迁移和增殖是由与Gq偶联的LPA受体介导的。
Cell Signal. 2006 Oct;18(10):1695-701. doi: 10.1016/j.cellsig.2006.01.009. Epub 2006 Feb 28.
8
Lysophosphatidic acid stimulates cell growth by different mechanisms in SKOV-3 and Caov-3 ovarian cancer cells: distinct roles for Gi- and Rho-dependent pathways.溶血磷脂酸通过不同机制刺激SKOV-3和Caov-3卵巢癌细胞的生长：Gi和Rho依赖性途径的不同作用。
Pharmacology. 2009;83(6):333-47. doi: 10.1159/000217582. Epub 2009 May 7.
9
Autotaxin and LPA1 and LPA5 receptors exert disparate functions in tumor cells versus the host tissue microenvironment in melanoma invasion and metastasis.自分泌运动因子以及溶血磷脂酸1和溶血磷脂酸5受体在黑色素瘤侵袭和转移过程中，在肿瘤细胞与宿主组织微环境中发挥不同的功能。
Mol Cancer Res. 2015 Jan;13(1):174-85. doi: 10.1158/1541-7786.MCR-14-0263. Epub 2014 Aug 26.
10
G(q)-dependent signalling by the lysophosphatidic acid receptor LPA(3) in gastric smooth muscle: reciprocal regulation of MYPT1 phosphorylation by Rho kinase and cAMP-independent PKA.溶血磷脂酸受体LPA(3)在胃平滑肌中通过G(q)依赖性信号传导：Rho激酶和非cAMP依赖性蛋白激酶A对肌球蛋白磷酸酶靶亚基1（MYPT1）磷酸化的相互调节
Biochem J. 2008 May 1;411(3):543-51. doi: 10.1042/bj20071299.

引用本文的文献

1
A Reliable System for Quantitative G-Protein Activation Imaging in Cancer Cells.一种用于癌细胞中 G 蛋白激活定量成像的可靠系统。
Cells. 2024 Jun 27;13(13):1114. doi: 10.3390/cells13131114.
2
A combined opposite targeting of p110δ PI3K and RhoA abrogates skin cancer.联合靶向抑制 p110δ PI3K 和 RhoA 可消除皮肤癌。
Commun Biol. 2024 Jan 5;7(1):26. doi: 10.1038/s42003-023-05639-8.
3
Emerging roles of lysophosphatidic acid receptor subtype 5 (LPAR5) in inflammatory diseases and cancer.溶血磷脂酸受体亚型 5（LPAR5）在炎症性疾病和癌症中的新兴作用。

本文引用的文献

1
Autotaxin and LPA receptor signaling in cancer.自分泌酶和 LPA 受体信号在癌症中的作用。
Cancer Metastasis Rev. 2011 Dec;30(3-4):557-65. doi: 10.1007/s10555-011-9319-7.
2
LPA5 is abundantly expressed by human mast cells and important for lysophosphatidic acid induced MIP-1β release.LPA5 在人肥大细胞中大量表达，对于溶血磷脂酸诱导的 MIP-1β 释放很重要。
PLoS One. 2011 Mar 28;6(3):e18192. doi: 10.1371/journal.pone.0018192.
3
GPR92/LPA₅ lysophosphatidate receptor mediates megakaryocytic cell shape change induced by human atherosclerotic plaques.
Pharmacol Ther. 2023 May;245:108414. doi: 10.1016/j.pharmthera.2023.108414. Epub 2023 Apr 13.
4
Infiltration of LPAR5 macrophages in osteosarcoma tumor microenvironment predicts better outcomes.LPAR5 巨噬细胞浸润骨肉瘤肿瘤微环境预示着更好的预后。
Front Immunol. 2022 Dec 15;13:909932. doi: 10.3389/fimmu.2022.909932. eCollection 2022.
5
LPAR5 confers radioresistance to cancer cells associated with EMT activation via the ERK/Snail pathway.LPAR5 通过 ERK/Snail 通路赋予 EMT 激活相关的癌细胞放射抗性。
J Transl Med. 2022 Oct 5;20(1):456. doi: 10.1186/s12967-022-03673-4.
6
G-protein coupled receptor, PI3K and Rho signaling pathways regulate the cascades of Tau and amyloid-β in Alzheimer's disease.G蛋白偶联受体、PI3K和Rho信号通路调节阿尔茨海默病中Tau蛋白和β-淀粉样蛋白的级联反应。
Mol Biomed. 2021 Jun 10;2(1):17. doi: 10.1186/s43556-021-00036-1.
7
Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8 T cells.自分泌酶通过抑制趋化作用和 CD8 T 细胞的肿瘤浸润来阻碍抗肿瘤免疫。
Cell Rep. 2021 Nov 16;37(7):110013. doi: 10.1016/j.celrep.2021.110013.
8
A Forgotten Corner in Cancer Immunotherapy: The Role of Lipids.癌症免疫疗法中被遗忘的角落：脂质的作用
Front Oncol. 2021 Oct 14;11:751086. doi: 10.3389/fonc.2021.751086. eCollection 2021.
9
2-Carba-lysophosphatidic acid is a novel β-lysophosphatidic acid analogue with high potential for lysophosphatidic acid receptor activation and autotaxin inhibition.2- carb- 溶血磷脂酸是一种新型的 β-溶血磷脂酸类似物，具有高潜力激活溶血磷脂酸受体和抑制自分泌运动因子。
Sci Rep. 2021 Aug 30;11(1):17360. doi: 10.1038/s41598-021-96931-2.
10
Lysophosphatidic Acid Signaling in Cancer Cells: What Makes LPA So Special?溶血磷脂酸信号在癌细胞中的作用：是什么让 LPA 如此特别？
Cells. 2021 Aug 11;10(8):2059. doi: 10.3390/cells10082059.
GPR92/LPA₅ 溶血磷脂酸受体介导人动脉粥样硬化斑块诱导的巨核细胞形态变化。
Cardiovasc Res. 2011 Apr 1;90(1):157-64. doi: 10.1093/cvr/cvq369. Epub 2010 Nov 23.
4
International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature.国际基础和临床药理学联合会. LXXVIII. 溶血磷脂受体命名.
Pharmacol Rev. 2010 Dec;62(4):579-87. doi: 10.1124/pr.110.003111.
5
A genome-wide RNAi screen identifies multiple RSK-dependent regulators of cell migration.全基因组 RNAi 筛选鉴定出多个依赖 RSK 的细胞迁移调控因子。
Genes Dev. 2010 Dec 1;24(23):2654-65. doi: 10.1101/gad.1989110. Epub 2010 Nov 9.
6
Protein kinase B (PKB/Akt), a key mediator of the PI3K signaling pathway.蛋白激酶 B（PKB/Akt），是 PI3K 信号通路的关键介质。
Curr Top Microbiol Immunol. 2010;346:31-56. doi: 10.1007/82_2010_58.
7
Cancer cell expression of autotaxin controls bone metastasis formation in mouse through lysophosphatidic acid-dependent activation of osteoclasts.癌 细 胞 表 达 的 自 动 血 栓 溶 酶 原 控 制 了 骨 转 移 在 小 鼠 中 的 形 成，通 过 磷 脂 酸 依 赖 性 激 活 破 骨 细 胞。
PLoS One. 2010 Mar 17;5(3):e9741. doi: 10.1371/journal.pone.0009741.
8
LPA receptors: subtypes and biological actions.LPA 受体：亚型与生物学作用。
Annu Rev Pharmacol Toxicol. 2010;50:157-86. doi: 10.1146/annurev.pharmtox.010909.105753.
9
cAMP-dependent axon guidance is distinctly regulated by Epac and protein kinase A.cAMP 依赖性轴突导向受 Epac 和蛋白激酶 A 的调控。
J Neurosci. 2009 Dec 9;29(49):15434-44. doi: 10.1523/JNEUROSCI.3071-09.2009.
10
Elevation of intracellular cyclic AMP inhibits NF-kappaB-mediated thymosin beta4 expression in melanoma cells.细胞内环磷酸腺苷水平的升高抑制黑色素瘤细胞中 NF-κB 介导的胸腺素β4 表达。
Exp Cell Res. 2009 Nov 15;315(19):3325-35. doi: 10.1016/j.yexcr.2009.05.024. Epub 2009 Jun 3.