Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway

Journal of Cell Biology - Tập 195 Số 5 - Trang 903-920 - 2011
Marco Magalhaes1,2,3, Daniel R. Larson4, Christopher C. Mader5,6, Jose Javier Bravo‐Cordero1,2,3, Hava Gil-Henn5,6, Matthew G. Oser2,3, Xiaohong Chen2,3, Anthony J. Koleske5,6, John S. Condeelis1,2,3
1Department of Anatomy and Structural Biology 1 and 2
2Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461
3Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461 1 and 2
4National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
5Department of Cell Biology and Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520
6Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 4 and 5

Tóm tắt

Invadopodia are invasive protrusions with proteolytic activity uniquely found in tumor cells. Cortactin phosphorylation is a key step during invadopodia maturation, regulating Nck1 binding and cofilin activity. The precise mechanism of cortactin-dependent cofilin regulation and the roles of this pathway in invadopodia maturation and cell invasion are not fully understood. We provide evidence that cortactin–cofilin binding is regulated by local pH changes at invadopodia that are mediated by the sodium–hydrogen exchanger NHE1. Furthermore, cortactin tyrosine phosphorylation mediates the recruitment of NHE1 to the invadopodium compartment, where it locally increases the pH to cause the release of cofilin from cortactin. We show that this mechanism involving cortactin phosphorylation, local pH increase, and cofilin activation regulates the dynamic cycles of invadopodium protrusion and retraction and is essential for cell invasion in 3D. Together, these findings identify a novel pH-dependent regulation of cell invasion.

Từ khóa


Tài liệu tham khảo

Aharonovitz, 2000, Intracellular pH regulation by Na(+)/H(+) exchange requires phosphatidylinositol 4,5-bisphosphate, J. Cell Biol., 150, 213, 10.1083/jcb.150.1.213

Artym, 2006, Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function, Cancer Res., 66, 3034, 10.1158/0008-5472.CAN-05-2177

Artym, 2011, Dynamic membrane remodeling at invadopodia differentiates invadopodia from podosomes, Eur. J. Cell Biol., 90, 172, 10.1016/j.ejcb.2010.06.006

Ayala, 2008, Multiple regulatory inputs converge on cortactin to control invadopodia biogenesis and extracellular matrix degradation, J. Cell Sci., 121, 369, 10.1242/jcs.008037

Bailly, 2003, Polarised migration: cofilin holds the front, Curr. Biol., 13, R128, 10.1016/S0960-9822(03)00072-1

Blouw, 2008, A role for the podosome/invadopodia scaffold protein Tks5 in tumor growth in vivo, Eur. J. Cell Biol., 87, 555, 10.1016/j.ejcb.2008.02.008

Bourguignon, 2004, CD44 interaction with Na+-H+ exchanger (NHE1) creates acidic microenvironments leading to hyaluronidase-2 and cathepsin B activation and breast tumor cell invasion, J. Biol. Chem., 279, 26991, 10.1074/jbc.M311838200

Bowden, 2006, Co-localization of cortactin and phosphotyrosine identifies active invadopodia in human breast cancer cells, Exp. Cell Res., 312, 1240, 10.1016/j.yexcr.2005.12.012

Bryce, 2005, Cortactin promotes cell motility by enhancing lamellipodial persistence, Curr. Biol., 15, 1276, 10.1016/j.cub.2005.06.043

Busco, 2010, NHE1 promotes invadopodial ECM proteolysis through acidification of the peri-invadopodial space, FASEB J., 24, 3903, 10.1096/fj.09-149518

Cao, 2006, Energetics and kinetics of cooperative cofilin-actin filament interactions, J. Mol. Biol., 361, 257, 10.1016/j.jmb.2006.06.019

Cardone, 2005, Protein kinase A gating of a pseudopodial-located RhoA/ROCK/p38/NHE1 signal module regulates invasion in breast cancer cell lines, Mol. Biol. Cell., 16, 3117, 10.1091/mbc.E04-10-0945

Cardone, 2007, The NHERF1 PDZ2 domain regulates PKA-RhoA-p38-mediated NHE1 activation and invasion in breast tumor cells, Mol. Biol. Cell., 18, 1768, 10.1091/mbc.E06-07-0617

Carlier, 1997, Actin depolymerizing factor (ADF/cofilin) enhances the rate of filament turnover: implication in actin-based motility, J. Cell Biol., 136, 1307, 10.1083/jcb.136.6.1307

Chaillet, 1985, Intracellular calibration of a pH-sensitive dye in isolated, perfused salamander proximal tubules, J. Gen. Physiol., 86, 765, 10.1085/jgp.86.6.765

Chan, 2000, Role of cofilin in epidermal growth factor-stimulated actin polymerization and lamellipod protrusion, J. Cell Biol., 148, 531, 10.1083/jcb.148.3.531

Chen, 1989, Proteolytic activity of specialized surface protrusions formed at rosette contact sites of transformed cells, J. Exp. Zool., 251, 167, 10.1002/jez.1402510206

Clark, 2008, A new role for cortactin in invadopodia: regulation of protease secretion, Eur. J. Cell Biol., 87, 581, 10.1016/j.ejcb.2008.01.008

Clark, 2007, Cortactin is an essential regulator of matrix metalloproteinase secretion and extracellular matrix degradation in invadopodia, Cancer Res., 67, 4227, 10.1158/0008-5472.CAN-06-3928

Crimaldi, 2009, Tks5 recruits AFAP-110, p190RhoGAP, and cortactin for podosome formation, Exp. Cell Res., 315, 2581, 10.1016/j.yexcr.2009.06.012

Crocker, 1996, Methods of digital video microscopy for colloidal studies, J. Colloid Interface Sci., 179, 298, 10.1006/jcis.1996.0217

Denker, 2002, Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1, J. Cell Biol., 159, 1087, 10.1083/jcb.200208050

Denker, 2000, Direct binding of the Na—H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell shape independently of H(+) translocation, Mol. Cell., 6, 1425, 10.1016/S1097-2765(00)00139-8

DesMarais, 2004, Synergistic interaction between the Arp2/3 complex and cofilin drives stimulated lamellipod extension, J. Cell Sci., 117, 3499, 10.1242/jcs.01211

DesMarais, 2005, Cofilin takes the lead, J. Cell Sci., 118, 19, 10.1242/jcs.01631

DesMarais, 2009, N-WASP and cortactin are involved in invadopodium-dependent chemotaxis to EGF in breast tumor cells, Cell Motil. Cytoskeleton., 66, 303, 10.1002/cm.20361

Feige, 2005, PixFRET, an ImageJ plug-in for FRET calculation that can accommodate variations in spectral bleed-throughs, Microsc. Res. Tech., 68, 51, 10.1002/jemt.20215

Frantz, 2007, Positive feedback between Cdc42 activity and H+ efflux by the Na-H exchanger NHE1 for polarity of migrating cells, J. Cell Biol., 179, 403, 10.1083/jcb.200704169

Frantz, 2008, Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding, J. Cell Biol., 183, 865, 10.1083/jcb.200804161

Ghosh, 2004, Cofilin promotes actin polymerization and defines the direction of cell motility, Science., 304, 743, 10.1126/science.1094561

Gimona, 2008, Assembly and biological role of podosomes and invadopodia, Curr. Opin. Cell Biol., 20, 235, 10.1016/j.ceb.2008.01.005

Ichetovkin, 2002, Cofilin produces newly polymerized actin filaments that are preferred for dendritic nucleation by the Arp2/3 complex, Curr. Biol., 12, 79, 10.1016/S0960-9822(01)00629-7

Kaplan, 1994, Long-term expression of c-H-ras stimulates Na-H and Na(+)-dependent Cl-HCO3 exchange in NIH-3T3 fibroblasts, J. Biol. Chem., 269, 4116, 10.1016/S0021-9258(17)41751-0

Kemp, 2008, Structure and function of the human Na+/H+ exchanger isoform 1, Channels (Austin)., 2, 329, 10.4161/chan.2.5.6898

Khaled, 2001, Trophic factor withdrawal: p38 mitogen-activated protein kinase activates NHE1, which induces intracellular alkalinization, Mol. Cell. Biol., 21, 7545, 10.1128/MCB.21.22.7545-7557.2001

King, 1994, Regulation of the Ascaris major sperm protein (MSP) cytoskeleton by intracellular pH, Cell Motil. Cytoskeleton., 27, 193, 10.1002/cm.970270302

Kirkbride, 2011, Cortactin: a multifunctional regulator of cellular invasiveness, Cell Adh Migr., 5, 187, 10.4161/cam.5.2.14773

Lapetina, 2009, Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion, J. Cell Biol., 185, 503, 10.1083/jcb.200809085

Larson, 2005, Visualization of retrovirus budding with correlated light and electron microscopy, Proc. Natl. Acad. Sci. USA., 102, 15453, 10.1073/pnas.0504812102

Leyman, 2009, Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs cell steering, Mol. Biol. Cell., 20, 4509, 10.1091/mbc.E09-02-0121

Li, 2001, Cortactin potentiates bone metastasis of breast cancer cells, Cancer Res., 61, 6906

Li, 2010, The actin-bundling protein fascin stabilizes actin in invadopodia and potentiates protrusive invasion, Curr. Biol., 20, 339, 10.1016/j.cub.2009.12.035

Linder, 2007, The matrix corroded: podosomes and invadopodia in extracellular matrix degradation, Trends Cell Biol., 17, 107, 10.1016/j.tcb.2007.01.002

Lovy-Wheeler, 2006, Oscillatory increases in alkalinity anticipate growth and may regulate actin dynamics in pollen tubes of lily, Plant Cell., 18, 2182, 10.1105/tpc.106.044867

Mader, 2011, An EGFR-Src-Arg-cortactin pathway mediates functional maturation of invadopodia and breast cancer cell invasion, Cancer Res., 71, 1730, 10.1158/0008-5472.CAN-10-1432

Meima, 2009, The sodium-hydrogen exchanger NHE1 is an Akt substrate necessary for actin filament reorganization by growth factors, J. Biol. Chem., 284, 26666, 10.1074/jbc.M109.019448

Moriyama, 1996, Phosphorylation of Ser-3 of cofilin regulates its essential function on actin, Genes Cells., 1, 73, 10.1046/j.1365-2443.1996.05005.x

Oser, 2009, The cofilin activity cycle in lamellipodia and invadopodia, J. Cell. Biochem., 108, 1252, 10.1002/jcb.22372

Oser, 2009, Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation, J. Cell Biol., 186, 571, 10.1083/jcb.200812176

Oser, 2010, Specific tyrosine phosphorylation sites on cortactin regulate Nck1-dependent actin polymerization in invadopodia, J. Cell Sci., 123, 3662, 10.1242/jcs.068163

Packard, 2009, Direct visualization of protease activity on cells migrating in three-dimensions, Matrix Biol., 28, 3, 10.1016/j.matbio.2008.10.001

Poincloux, 2011, Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel, Proc. Natl. Acad. Sci. USA., 108, 1943, 10.1073/pnas.1010396108

Pollard, 1986, Actin and actin-binding proteins. A critical evaluation of mechanisms and functions, Annu. Rev. Biochem., 55, 987, 10.1146/annurev.bi.55.070186.005011

Putney, 2002, The changing face of the Na+/H+ exchanger, NHE1: structure, regulation, and cellular actions, Annu. Rev. Pharmacol. Toxicol., 42, 527, 10.1146/annurev.pharmtox.42.092001.143801

Reshkin, 2000, Phosphoinositide 3-kinase is involved in the tumor-specific activation of human breast cancer cell Na(+)/H(+) exchange, motility, and invasion induced by serum deprivation, J. Biol. Chem., 275, 5361, 10.1074/jbc.275.8.5361

Sabeh, 2009, Protease-dependent versus -independent cancer cell invasion programs: three-dimensional amoeboid movement revisited, J. Cell Biol., 185, 11, 10.1083/jcb.200807195

Schoumacher, 2010, Actin, microtubules, and vimentin intermediate filaments cooperate for elongation of invadopodia, J. Cell Biol., 189, 541, 10.1083/jcb.200909113

Sidani, 2007, Cofilin determines the migration behavior and turning frequency of metastatic cancer cells, J. Cell Biol., 179, 777, 10.1083/jcb.200707009

Stock, 2009, Protons make tumor cells move like clockwork, Pflugers Arch., 458, 981, 10.1007/s00424-009-0677-8

Stock, 2005, Migration of human melanoma cells depends on extracellular pH and Na+/H+ exchange, J. Physiol., 567, 225, 10.1113/jphysiol.2005.088344

Stock, 2008, Protons extruded by NHE1: digestive or glue?, Eur. J. Cell Biol., 87, 591, 10.1016/j.ejcb.2008.01.007

Stüwe, 2007, pH dependence of melanoma cell migration: protons extruded by NHE1 dominate protons of the bulk solution, J. Physiol., 585, 351, 10.1113/jphysiol.2007.145185

Stylli, 2009, Nck adaptor proteins link Tks5 to invadopodia actin regulation and ECM degradation, J. Cell Sci., 122, 2727, 10.1242/jcs.046680

Sun, 2007, Rac1 and Rac2 differentially regulate actin free barbed end formation downstream of the fMLP receptor, J. Cell Biol., 179, 239, 10.1083/jcb.200705122

Takino, 2006, Membrane-type 1 matrix metalloproteinase modulates focal adhesion stability and cell migration, Exp. Cell Res., 312, 1381, 10.1016/j.yexcr.2006.01.008

Tania, 2011, A temporal model of cofilin regulation and the early peak of actin barbed ends in invasive tumor cells, Biophys. J., 100, 1883, 10.1016/j.bpj.2011.02.036

Tehrani, 2007, Src phosphorylation of cortactin enhances actin assembly, Proc. Natl. Acad. Sci. USA., 104, 11933, 10.1073/pnas.0701077104

Thompson, 2002, Precise nanometer localization analysis for individual fluorescent probes, Biophys. J., 82, 2775, 10.1016/S0006-3495(02)75618-X

Tolde, 2010, The structure of invadopodia in a complex 3D environment, Eur. J. Cell Biol., 89, 674, 10.1016/j.ejcb.2010.04.003

Tominaga, 1998, Na-H exchange acts downstream of RhoA to regulate integrin-induced cell adhesion and spreading, Mol. Biol. Cell., 9, 2287, 10.1091/mbc.9.8.2287

Uruno, 2001, Activation of Arp2/3 complex-mediated actin polymerization by cortactin, Nat. Cell Biol., 3, 259, 10.1038/35060051

Van Goethem, 2010, Matrix architecture dictates three-dimensional migration modes of human macrophages: differential involvement of proteases and podosome-like structures, J. Immunol., 184, 1049, 10.4049/jimmunol.0902223

van Rheenen, 2007, EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells, J. Cell Biol., 179, 1247, 10.1083/jcb.200706206

van Rheenen, 2009, A common cofilin activity cycle in invasive tumor cells and inflammatory cells, J. Cell Sci., 122, 305, 10.1242/jcs.031146

Wang, 2004, Identification and testing of a gene expression signature of invasive carcinoma cells within primary mammary tumors, Cancer Res., 64, 8585, 10.1158/0008-5472.CAN-04-1136

Wang, 2007, The cofilin pathway in breast cancer invasion and metastasis, Nat. Rev. Cancer., 7, 429, 10.1038/nrc2148

Weaver, 2006, Invadopodia: specialized cell structures for cancer invasion, Clin. Exp. Metastasis., 23, 97, 10.1007/s10585-006-9014-1

Weaver, 2008, Cortactin in tumor invasiveness, Cancer Lett., 265, 157, 10.1016/j.canlet.2008.02.066

Weaver, 2001, Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation, Curr. Biol., 11, 370, 10.1016/S0960-9822(01)00098-7

Weed, 2001, Cortactin: coupling membrane dynamics to cortical actin assembly, Oncogene., 20, 6418, 10.1038/sj.onc.1204783

Weed, 2000, Cortactin localization to sites of actin assembly in lamellipodia requires interactions with F-actin and the Arp2/3 complex, J. Cell Biol., 151, 29, 10.1083/jcb.151.1.29

Wohland, 2001, The standard deviation in fluorescence correlation spectroscopy, Biophys. J., 80, 2987, 10.1016/S0006-3495(01)76264-9

Wolf, 2003, Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis, J. Cell Biol., 160, 267, 10.1083/jcb.200209006

Wolf, 2009, Collagen-based cell migration models in vitro and in vivo, Semin. Cell Dev. Biol., 20, 931, 10.1016/j.semcdb.2009.08.005

Yamaguchi, 2007, Regulation of the actin cytoskeleton in cancer cell migration and invasion, Biochim. Biophys. Acta., 1773, 642, 10.1016/j.bbamcr.2006.07.001

Yamaguchi, 2005, Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin, J. Cell Biol., 168, 441, 10.1083/jcb.200407076

Yan, 2001, The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor, J. Biol. Chem., 276, 31349, 10.1074/jbc.M102679200