• 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

LMTK3 通过磷酸化 Rab 连接蛋白控制 EphA2 依赖 Rab14 的运输，促进细胞间的排斥。

Phosphorylation of Rab-coupling protein by LMTK3 controls Rab14-dependent EphA2 trafficking to promote cell:cell repulsion.

机构信息

CRUK Beatson Institute for Cancer Research, Garscube Estate, Glasgow G61 1BD, UK.

Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.

出版信息

Nat Commun. 2017 Mar 15;8:14646. doi: 10.1038/ncomms14646.

DOI:10.1038/ncomms14646
PMID:28294115
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5355957/
Abstract

The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis in vivo is unclear. Here we identify an RTK of the Eph family, EphA2, to be a cargo of an RCP-regulated endocytic pathway which controls cell:cell repulsion and metastasis in vivo. Phosphorylation of RCP at Ser by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart. Genetic disruption of RCP or EphA2 opposes cell:cell repulsion and metastasis in an autochthonous mouse model of pancreatic adenocarcinoma-whereas conditional knockout of another RCP cargo, α5 integrin, does not suppress pancreatic cancer metastasis-indicating a role for RCP-dependent trafficking of an Eph receptor to drive tumour dissemination in vivo.

摘要

Rab GTPase 效应因子 Rab 衔接蛋白 (RCP) 可通过控制整合素和受体酪氨酸激酶 (RTK) 的运输来促进体外侵袭行为，但 RCP 如何影响体内转移尚不清楚。在这里，我们确定 Eph 家族的一个 RTK，EphA2，是 RCP 调控的内吞途径的货物，该途径控制细胞：体内细胞排斥和转移。Lemur 酪氨酸激酶-3 (LMTK3) 对 RCP 的 Ser 磷酸化和 Akt 对 EphA2 的 Ser 磷酸化都有助于促进 Rab14 依赖性（和 Rab11 独立性）的 EphA2 运输，从而产生细胞：驱动肿瘤细胞分离的排斥事件。在胰腺腺癌细胞的同源小鼠模型中，RCP 或 EphA2 的遗传破坏会反对细胞：排斥和转移-而另一个 RCP 货物 α5 整合素的条件敲除不会抑制胰腺癌细胞转移-表明 Eph 受体依赖 RCP 的运输在体内驱动肿瘤播散。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/00ef07010869/ncomms14646-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/2d5633793ab1/ncomms14646-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/c24aa5204c05/ncomms14646-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/6487178cdafb/ncomms14646-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/a4b40372abe2/ncomms14646-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/f60fb14eb8be/ncomms14646-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/12dbaba0fa0b/ncomms14646-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/a04f6bc2dd6a/ncomms14646-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/00ef07010869/ncomms14646-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/2d5633793ab1/ncomms14646-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/c24aa5204c05/ncomms14646-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/6487178cdafb/ncomms14646-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/a4b40372abe2/ncomms14646-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/f60fb14eb8be/ncomms14646-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/12dbaba0fa0b/ncomms14646-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/a04f6bc2dd6a/ncomms14646-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e6d/5355957/00ef07010869/ncomms14646-f8.jpg

相似文献

1
Phosphorylation of Rab-coupling protein by LMTK3 controls Rab14-dependent EphA2 trafficking to promote cell:cell repulsion.LMTK3 通过磷酸化 Rab 连接蛋白控制 EphA2 依赖 Rab14 的运输，促进细胞间的排斥。
Nat Commun. 2017 Mar 15;8:14646. doi: 10.1038/ncomms14646.
2
Structure-Function Analyses of the Interactions between Rab11 and Rab14 Small GTPases with Their Shared Effector Rab Coupling Protein (RCP).Rab11和Rab14小GTP酶与其共同效应器Rab偶联蛋白（RCP）相互作用的结构-功能分析
J Biol Chem. 2015 Jul 24;290(30):18817-32. doi: 10.1074/jbc.M114.612366. Epub 2015 May 31.
3
Rab-coupling protein coordinates recycling of alpha5beta1 integrin and EGFR1 to promote cell migration in 3D microenvironments.Rab 偶联蛋白协调α5β1整合素和表皮生长因子受体1的再循环，以促进细胞在三维微环境中的迁移。
J Cell Biol. 2008 Oct 6;183(1):143-55. doi: 10.1083/jcb.200804140.
4
Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration.二酰基甘油激酶 α 控制 RCP 依赖性整合素运输以促进侵袭性迁移。
J Cell Biol. 2012 Jan 23;196(2):277-95. doi: 10.1083/jcb.201109112.
5
LMTK3 regulation of EV biogenesis and cargo sorting promotes tumour growth by reducing monocyte infiltration and driving pro-tumourigenic macrophage polarisation in breast cancer.LMTK3对细胞外囊泡生物发生和货物分选的调控通过减少单核细胞浸润和驱动乳腺癌中促肿瘤巨噬细胞极化来促进肿瘤生长。
Mol Cancer. 2025 May 23;24(1):149. doi: 10.1186/s12943-025-02346-2.
6
The RCP-Rab11 complex regulates endocytic protein sorting.RCP-Rab11复合体调节内吞蛋白分选。
Mol Biol Cell. 2004 Aug;15(8):3530-41. doi: 10.1091/mbc.e03-12-0918. Epub 2004 Jun 4.
7
Rab11 and its effector Rab coupling protein contribute to the trafficking of beta 1 integrins during axon growth in adult dorsal root ganglion neurons and PC12 cells.Rab11 及其效应因子 Rab 衔接蛋白在成年背根神经节神经元和 PC12 细胞轴突生长过程中β 1 整联蛋白的运输中发挥作用。
J Neurosci. 2010 Sep 1;30(35):11654-69. doi: 10.1523/JNEUROSCI.2425-10.2010.
8
Kinase-dependent and -independent roles of EphA2 in the regulation of prostate cancer invasion and metastasis.EphA2在前列腺癌侵袭和转移调控中的激酶依赖性及非依赖性作用
Am J Pathol. 2009 Apr;174(4):1492-503. doi: 10.2353/ajpath.2009.080473. Epub 2009 Mar 5.
9
Tyrosine kinase activity of EphA2 promotes its S897 phosphorylation and glioblastoma cell proliferation.EphA2 的酪氨酸激酶活性促进其 S897 磷酸化和神经胶质瘤细胞增殖。
Biochem Biophys Res Commun. 2018 May 23;499(4):920-926. doi: 10.1016/j.bbrc.2018.04.020. Epub 2018 Apr 9.
10
Characterisation of the Rab binding properties of Rab coupling protein (RCP) by site-directed mutagenesis.通过定点诱变对Rab偶联蛋白（RCP）的Rab结合特性进行表征。
FEBS Lett. 2004 Jul 30;571(1-3):86-92. doi: 10.1016/j.febslet.2004.06.068.

引用本文的文献

1
Targeting the secretory program of 3q-amplified lung cancers.靶向3q扩增肺癌的分泌程序。
J Clin Invest. 2024 Jun 17;134(12):e181798. doi: 10.1172/JCI181798.
2
The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.神经退行性疾病中神经元功能和紊乱的狐猴尾巴激酶家族。
Cell Mol Life Sci. 2024 Nov 9;81(1):447. doi: 10.1007/s00018-024-05480-0.
3
Eph receptors and ephrins in cancer progression.Eph 受体及其配体在癌症进展中的作用。

本文引用的文献

1
Rab11-FIP1C Is a Critical Negative Regulator in ErbB2-Mediated Mammary Tumor Progression.Rab11-FIP1C是ErbB2介导的乳腺肿瘤进展中的关键负调节因子。
Cancer Res. 2016 May 1;76(9):2662-74. doi: 10.1158/0008-5472.CAN-15-2782. Epub 2016 Mar 1.
2
Ubiquitination switches EphA2 vesicular traffic from a continuous safeguard to a finite signalling mode.泛素化将 EphA2 的囊泡运输从持续的保护机制转变为有限的信号传导模式。
Nat Commun. 2015 Aug 21;6:8047. doi: 10.1038/ncomms9047.
3
Prognostic role of lemur tyrosine kinase 3 in postoperative gastric cancer.
Nat Rev Cancer. 2024 Jan;24(1):5-27. doi: 10.1038/s41568-023-00634-x. Epub 2023 Nov 23.
4
microRNA-205 represses breast cancer metastasis by perturbing the rab coupling protein [RCP]-mediated integrin β1 recycling on the membrane.微小RNA-205通过干扰膜上Rab偶联蛋白（RCP）介导的整合素β1循环来抑制乳腺癌转移。
Apoptosis. 2024 Feb;29(1-2):191-209. doi: 10.1007/s10495-023-01912-7. Epub 2023 Nov 9.
5
MiR-214-3p targets Ras-related protein 14 (RAB14) to inhibit cellular migration and invasion in esophageal Cancer cells.miR-214-3p 通过靶向 Ras 相关蛋白 14（RAB14）抑制食管癌细胞的迁移和侵袭。
BMC Cancer. 2022 Dec 5;22(1):1265. doi: 10.1186/s12885-022-10304-0.
6
Rab11FIP1-deficient mice develop spontaneous inflammation and show increased susceptibility to colon damage.Rab11FIP1 缺陷小鼠发生自发性炎症，并表现出对结肠损伤的易感性增加。
Am J Physiol Gastrointest Liver Physiol. 2022 Sep 1;323(3):G239-G254. doi: 10.1152/ajpgi.00042.2022. Epub 2022 Jul 12.
7
Rab11-FIP1/RCP Functions as a Major Signalling Hub in the Oncogenic Roles of Mutant p53 in Cancer.Rab11-FIP1/RCP在癌症中突变型p53的致癌作用中作为主要信号枢纽发挥作用。
Front Oncol. 2021 Dec 21;11:804107. doi: 10.3389/fonc.2021.804107. eCollection 2021.
8
TP53 mutations upregulate RCP expression via Sp1/3 to drive lung cancer progression.TP53 突变通过 Sp1/Sp3 上调 RCP 的表达，从而驱动肺癌的进展。
Oncogene. 2022 Apr;41(16):2357-2371. doi: 10.1038/s41388-022-02260-7. Epub 2022 Mar 7.
9
Nuclear-capture of endosomes depletes nuclear G-actin to promote SRF/MRTF activation and cancer cell invasion.核内体的核捕获会耗尽核 G 肌动蛋白，从而促进 SRF/MRTF 的激活和癌细胞的侵袭。
Nat Commun. 2021 Nov 24;12(1):6829. doi: 10.1038/s41467-021-26839-y.
10
Rab11-FIP1 and Rab11-FIP5 Regulate pIgR/pIgA Transcytosis through TRIM21-Mediated Polyubiquitination.Rab11-FIP1 和 Rab11-FIP5 通过 TRIM21 介导的多泛素化调节 pIgR/pIgA 转胞运输。
Int J Mol Sci. 2021 Sep 28;22(19):10466. doi: 10.3390/ijms221910466.
狐猴酪氨酸激酶3在胃癌术后的预后作用
Mol Clin Oncol. 2014 Sep;2(5):756-760. doi: 10.3892/mco.2014.301. Epub 2014 Jun 3.
4
The kinase LMTK3 promotes invasion in breast cancer through GRB2-mediated induction of integrin β₁.激酶LMTK3通过GRB2介导的整合素β₁诱导促进乳腺癌侵袭。
Sci Signal. 2014 Jun 17;7(330):ra58. doi: 10.1126/scisignal.2005170.
5
EphA receptors regulate prostate cancer cell dissemination through Vav2-RhoA mediated cell-cell repulsion.EphA 受体通过 Vav2-RhoA 介导的细胞-细胞排斥作用调节前列腺癌细胞的扩散。
Biol Open. 2014 May 2;3(6):453-62. doi: 10.1242/bio.20146601.
6
LMTK3 deficiency causes pronounced locomotor hyperactivity and impairs endocytic trafficking.LMTK3 缺失导致明显的运动过度活跃，并损害内吞运输。
J Neurosci. 2014 Apr 23;34(17):5927-37. doi: 10.1523/JNEUROSCI.1621-13.2014.
7
Endocytosis and cancer.内吞作用与癌症。
Cold Spring Harb Perspect Biol. 2013 Dec 1;5(12):a016949. doi: 10.1101/cshperspect.a016949.
8
EphA2 signaling following endocytosis: role of Tiam1.EphA2 信号转导：Tiam1 的作用。
Traffic. 2013 Dec;14(12):1255-71. doi: 10.1111/tra.12123. Epub 2013 Oct 10.
9
A central role for vesicle trafficking in epithelial neoplasia: intracellular highways to carcinogenesis.囊泡运输在上皮性肿瘤发生中的核心作用：致癌作用的细胞内高速公路。
Nat Rev Cancer. 2013 Nov;13(11):813-20. doi: 10.1038/nrc3601. Epub 2013 Oct 10.
10
EphA2 cleavage by MT1-MMP triggers single cancer cell invasion via homotypic cell repulsion.EphA2 的切割由 MT1-MMP 触发，通过同质细胞排斥作用引发单个癌细胞的侵袭。
J Cell Biol. 2013 Apr 29;201(3):467-84. doi: 10.1083/jcb.201205176.