CdGAP 调控细胞在二维和三维基质环境中的迁移和黏附动态。
CdGAP regulates cell migration and adhesion dynamics in two-and three-dimensional matrix environments.
机构信息
Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
出版信息
Cytoskeleton (Hoboken). 2012 Sep;69(9):644-58. doi: 10.1002/cm.21057. Epub 2012 Aug 20.
Abstract
CdGAP is a Rac1/Cdc42 specific GTPase activating protein (GAP) that localizes to cell-matrix adhesions through an interaction with the adhesion scaffold α-parvin/actopaxin to regulate lamellipodia formation and cell spreading. Herein, we demonstrate, using a combination of siRNA-mediated silencing and overexpression, that cdGAP negatively regulates directed and random migration by controlling adhesion maturation and dynamics through the regulation of both adhesion assembly and disassembly. Interestingly, cdGAP was also localized to adhesions formed in three-dimensional (3D) matrix environments and cdGAP depletion promoted cancer cell migration and invasion through 3D matrices. These findings highlight the importance of GAP proteins in the regulation of Rho family GTPases and the coordination of the cell migration machinery..
摘要
CdGAP 是 Rac1/Cdc42 特异性 GTP 酶激活蛋白 (GAP)，通过与黏附支架 α-伴肌动蛋白/actopaxin 相互作用而定位到细胞-基质黏附处，从而调节片状伪足的形成和细胞铺展。在此，我们通过 siRNA 介导的沉默和过表达的组合，证明 cdGAP 通过控制黏附组装和拆卸来调节黏附成熟和动态，从而负调控定向和随机迁移。有趣的是，cdGAP 也定位于三维 (3D) 基质环境中形成的黏附处，cdGAP 耗竭通过 3D 基质促进癌细胞迁移和侵袭。这些发现强调了 GAP 蛋白在 Rho 家族 GTP 酶调节和细胞迁移机制协调中的重要性。
相似文献
1
CdGAP regulates cell migration and adhesion dynamics in two-and three-dimensional matrix environments.CdGAP 调控细胞在二维和三维基质环境中的迁移和黏附动态。
Cytoskeleton (Hoboken). 2012 Sep;69(9):644-58. doi: 10.1002/cm.21057. Epub 2012 Aug 20.
2
CdGAP associates with actopaxin to regulate integrin-dependent changes in cell morphology and motility.CdGAP与肌动蛋白结合蛋白相关联，以调节整合素依赖性的细胞形态和运动变化。
Curr Biol. 2006 Jul 25;16(14):1375-85. doi: 10.1016/j.cub.2006.05.057.
3
A stretch of polybasic residues mediates Cdc42 GTPase-activating protein (CdGAP) binding to phosphatidylinositol 3,4,5-trisphosphate and regulates its GAP activity.一段多碱性残基介导 Cdc42 GTP 酶激活蛋白（CdGAP）与磷脂酰肌醇 3,4,5-三磷酸结合，并调节其 GAP 活性。
J Biol Chem. 2012 Jun 1;287(23):19610-21. doi: 10.1074/jbc.M112.344606. Epub 2012 Apr 19.
4
The focal adhesion-localized CdGAP regulates matrix rigidity sensing and durotaxis.粘着斑定位的CdGAP调节基质硬度感知和趋硬性。
PLoS One. 2014 Mar 14;9(3):e91815. doi: 10.1371/journal.pone.0091815. eCollection 2014.
5
CdGAP is required for transforming growth factor β- and Neu/ErbB-2-induced breast cancer cell motility and invasion.CdGAP 对于转化生长因子 β 和 Neu/ErbB-2 诱导的乳腺癌细胞迁移和侵袭是必需的。
Oncogene. 2011 Mar 3;30(9):1032-45. doi: 10.1038/onc.2010.477. Epub 2010 Nov 1.
6
The human orthologue of CdGAP is a phosphoprotein and a GTPase-activating protein for Cdc42 and Rac1 but not RhoA.CdGAP的人类同源物是一种磷蛋白，是Cdc42和Rac1而非RhoA的GTP酶激活蛋白。
Biol Cell. 2006 Aug;98(8):445-56. doi: 10.1042/BC20050101.
7
Glycogen synthase kinase-3 phosphorylates CdGAP at a consensus ERK 1 regulatory site.糖原合酶激酶-3在一个共有ERK 1调节位点处使CdGAP磷酸化。
J Biol Chem. 2007 Feb 9;282(6):3624-31. doi: 10.1074/jbc.M610073200. Epub 2006 Dec 8.
8
The Cdc42/Rac1 regulator CdGAP is a novel E-cadherin transcriptional co-repressor with Zeb2 in breast cancer.Cdc42/Rac1调节因子CdGAP是一种在乳腺癌中与Zeb2共同作用的新型E-钙黏蛋白转录共抑制因子。
Oncogene. 2017 Jun 15;36(24):3490-3503. doi: 10.1038/onc.2016.492. Epub 2017 Jan 30.
9
Suppression of Slit2/Robo1 mediated HUVEC migration by Robo4.Robo4对Slit2/Robo1介导的人脐静脉内皮细胞迁移的抑制作用。
Biochem Biophys Res Commun. 2016 Jan 22;469(4):797-802. doi: 10.1016/j.bbrc.2015.12.075. Epub 2015 Dec 20.
10
The activity of the GTPase-activating protein CdGAP is regulated by the endocytic protein intersectin.GTP酶激活蛋白CdGAP的活性受内吞蛋白intersectin的调节。
J Biol Chem. 2002 Feb 22;277(8):6366-73. doi: 10.1074/jbc.M105516200. Epub 2001 Dec 13.
引用本文的文献
1
Rabenosyn-5 suppresses non-small cell lung cancer metastasis via inhibiting CDC42 activity.Rabenosyn-5 通过抑制 CDC42 活性抑制非小细胞肺癌转移。
Cancer Gene Ther. 2024 Oct;31(10):1465-1476. doi: 10.1038/s41417-024-00813-4. Epub 2024 Jul 29.
2
ARHGEF9 regulates melanoma morphogenesis in environments with diverse geometry and elasticity by promoting filopodial-driven adhesion.ARHGEF9通过促进丝状伪足驱动的黏附作用，在具有不同几何形状和弹性的环境中调节黑色素瘤的形态发生。
iScience. 2022 Aug 8;25(8):104795. doi: 10.1016/j.isci.2022.104795. eCollection 2022 Aug 19.
3
Fixing the GAP: The role of RhoGAPs in cancer.修复缺口：RhoGAPs 在癌症中的作用。
Eur J Cell Biol. 2022 Apr;101(2):151209. doi: 10.1016/j.ejcb.2022.151209. Epub 2022 Feb 10.
4
CdGAP promotes prostate cancer metastasis by regulating epithelial-to-mesenchymal transition, cell cycle progression, and apoptosis.CdGAP 通过调节上皮-间质转化、细胞周期进程和细胞凋亡促进前列腺癌转移。
Commun Biol. 2021 Sep 7;4(1):1042. doi: 10.1038/s42003-021-02520-4.
5
Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices.Hic-5 的表达是癌细胞在三维基质中形态、迁移和可塑性的主要指标。
Mol Biol Cell. 2018 Jul 15;29(13):1704-1717. doi: 10.1091/mbc.E18-02-0092. Epub 2018 May 17.
6
CdGAP/ARHGAP31 is regulated by RSK phosphorylation and binding to 14-3-3β adaptor protein.CdGAP/ARHGAP31受RSK磷酸化作用及与14-3-3β衔接蛋白结合的调控。
Oncotarget. 2018 Jan 10;9(14):11646-11664. doi: 10.18632/oncotarget.24126. eCollection 2018 Feb 20.
7
The scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts.支架蛋白 Ajuba 抑制上皮细胞中的 CdGAP 活性，以维持稳定的细胞-细胞接触。
Sci Rep. 2017 Aug 23;7(1):9249. doi: 10.1038/s41598-017-09024-4.
8
Paxillin: a crossroad in pathological cell migration.桩蛋白：病理性细胞迁移的一个关键节点。
J Hematol Oncol. 2017 Feb 18;10(1):50. doi: 10.1186/s13045-017-0418-y.
9
CdGAP/ARHGAP31, a Cdc42/Rac1 GTPase regulator, is critical for vascular development and VEGF-mediated angiogenesis.CdGAP/ARHGAP31，一种Cdc42/Rac1 GTP酶调节剂，对血管发育和VEGF介导的血管生成至关重要。
Sci Rep. 2016 Jun 7;6:27485. doi: 10.1038/srep27485.
10
The focal adhesion-localized CdGAP regulates matrix rigidity sensing and durotaxis.粘着斑定位的CdGAP调节基质硬度感知和趋硬性。
PLoS One. 2014 Mar 14;9(3):e91815. doi: 10.1371/journal.pone.0091815. eCollection 2014.
本文引用的文献
1
Micro-environmental control of cell migration--myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics.细胞迁移的微环境控制——肌球蛋白 IIA 通过控制细胞黏附动力学，对于在纤维环境中的有效迁移是必需的。
J Cell Sci. 2012 May 1;125(Pt 9):2244-56. doi: 10.1242/jcs.098806. Epub 2012 Feb 10.
2
Integrins in cell migration.整合素在细胞迁移中的作用。
Cold Spring Harb Perspect Biol. 2011 Sep 1;3(9):a005074. doi: 10.1101/cshperspect.a005074.
3
Cell-matrix adhesions in 3D.三维细胞-基质黏附。
Matrix Biol. 2011 Sep;30(7-8):363-8. doi: 10.1016/j.matbio.2011.06.001. Epub 2011 Jun 23.
4
Wound repair: toward understanding and integration of single-cell and multicellular wound responses.创伤修复：单细胞和多细胞创伤反应的理解与整合。
Annu Rev Cell Dev Biol. 2011;27:237-63. doi: 10.1146/annurev-cellbio-092910-154251. Epub 2011 Jun 20.
5
Pak1 regulates focal adhesion strength, myosin IIA distribution, and actin dynamics to optimize cell migration.Pak1 调节黏附强度、肌球蛋白 IIA 分布和肌动蛋白动力学，从而优化细胞迁移。
J Cell Biol. 2011 Jun 27;193(7):1289-303. doi: 10.1083/jcb.201010059.
6
SH3BP1, an exocyst-associated RhoGAP, inactivates Rac1 at the front to drive cell motility.SH3BP1，一种与外泌体相关的 RhoGAP，在前端失活 Rac1 以驱动细胞运动。
Mol Cell. 2011 Jun 10;42(5):650-61. doi: 10.1016/j.molcel.2011.03.032.
7
Gain-of-function mutations of ARHGAP31, a Cdc42/Rac1 GTPase regulator, cause syndromic cutis aplasia and limb anomalies.ARHGAP31 是一种 Cdc42/Rac1 GTP 酶调节因子，其功能获得性突变会导致综合征性皮肤发育不良和肢体异常。
Am J Hum Genet. 2011 May 13;88(5):574-85. doi: 10.1016/j.ajhg.2011.04.013.
8
Molecular architecture and function of matrix adhesions.基质黏附的分子结构与功能。
Cold Spring Harb Perspect Biol. 2011 May 1;3(5):a005033. doi: 10.1101/cshperspect.a005033.
9
Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation.肌球蛋白-II 反应性焦点黏附蛋白质组分析揭示 β-Pix 在焦点黏附成熟的负调控中的作用。
Nat Cell Biol. 2011 Apr;13(4):383-93. doi: 10.1038/ncb2216. Epub 2011 Mar 20.
10
Reducing background fluorescence reveals adhesions in 3D matrices.降低背景荧光可揭示三维基质中的粘连。
Nat Cell Biol. 2011 Jan;13(1):3-5; author reply 5-7. doi: 10.1038/ncb0111-3.
Zotero 插件