title: At the leading edge of three-dimensional cell migration.
abstract: Cells migrating on flat two-dimensional (2D) surfaces use actin polymerization to extend the leading edge of the plasma membrane during lamellipodia-based migration. This mode of migration is not universal; it represents only one of several mechanisms of cell motility in three-dimensional (3D) environments. The distinct modes of 3D migration are strongly dependent on the physical properties of the extracellular matrix, and they can be distinguished by the structure of the leading edge and the degree of matrix adhesion. How are these distinct modes of cell motility in 3D environments related to each other and regulated? Recent studies show that the same type of cell migrating in 3D extracellular matrix can switch between different leading edge structures. This mode-switching behavior, or plasticity, by a single cell suggests that the apparent diversity of motility mechanisms is integrated by a common intracellular signaling pathway that governs the mode of cell migration. In this Commentary, we propose that the mode of 3D cell migration is governed by a signaling axis involving cell-matrix adhesions, RhoA signaling and actomyosin contractility, and that this might represent a universal mechanism that controls 3D cell migration.
authors: Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. petrier@mail.nih.gov
authors: Ryan J
authors: RJ
authors: Petrie
authors: Kenneth M
authors: KM
authors: Yamada
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans
references: Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1943-8
references: 21245302
references: Nat Cell Biol. 2011 Jun;13(6):722-7
references: 21572419
references: Cell Motil Cytoskeleton. 1992;22(2):135-51
references: 1633624
references: Biophys J. 2000 Jul;79(1):144-52
references: 10866943
references: J Cell Sci. 1968 Dec;3(4):549-62
references: 5707852
references: Int Rev Cytol. 1994;150:35-68
references: 8169081
references: Cell. 1989 Jan 27;56(2):281-90
references: 2521461
references: J Cell Sci. 1997 Nov;110 ( Pt 22):2833-44
references: 9427291
references: J Cell Sci. 2012 May 1;125(Pt 9):2244-56
references: 22328520
references: Nat Rev Cancer. 2011 Oct 13;11(11):761-74
references: 21993244
references: Exp Cell Res. 1970 Mar;59(3):393-8
references: 4907703
references: Proc Natl Acad Sci U S A. 1976 Feb;73(2):544-8
references: 174110
references: Cell. 2012 Mar 2;148(5):973-87
references: 22385962
references: J Cell Biol. 2012 Apr 30;197(3):439-55
references: 22547408
references: Science. 2004 Sep 10;305(5690):1615-9
references: 15361624
references: Commun Integr Biol. 2012 Jan 1;5(1):71-3
references: 22482015
references: Oncogene. 2000 Jun 29;19(28):3156-63
references: 10918570
references: Dev Biol. 1982 Jul;92(1):107-22
references: 7106372
references: Cell Tissue Res. 2010 Jan;339(1):83-92
references: 19921267
references: Exp Cell Res. 1975 Oct 15;95(2):425-39
references: 1238279
references: Cancer Metastasis Rev. 2009 Jun;28(1-2):129-35
references: 19153672
references: Dev Cell. 2010 Aug 17;19(2):194-206
references: 20708583
references: Nature. 2009 Sep 3;461(7260):104-8
references: 19693014
references: Cell Motil Cytoskeleton. 1991;18(1):26-40
references: 1848484
references: Exp Cell Res. 1970 Jun;60(3):437-44
references: 5463639
references: Nature. 2005 May 19;435(7040):365-9
references: 15902261
references: J Cell Biol. 2003 Feb 3;160(3):409-21
references: 12566431
references: Dev Cell. 2012 Jul 17;23(1):210-8
references: 22705393
references: Cancer Res. 1980 Sep;40(9):3222-7
references: 7000340
references: Annu Rev Biophys Bioeng. 1978;7:469-95
references: 352246
references: Nat Cell Biol. 2010 Jun;12(6):591-7
references: 20473296
references: Curr Opin Cell Biol. 2010 Oct;22(5):690-6
references: 20829016
references: J Cell Sci. 2003 Apr 1;116(Pt 7):1157-73
references: 12615960
references: Mol Biol Cell. 2003 Feb;14(2):384-95
references: 12589041
references: Nature. 2008 May 1;453(7191):51-5
references: 18451854
references: Oncogene. 2006 Sep 21;25(42):5726-40
references: 16652152
references: Cell. 1992 Aug 7;70(3):389-99
references: 1643657
references: Nat Cell Biol. 2008 Feb;10(2):127-37
references: 18204440
references: J Cell Biol. 2002 Dec 23;159(6):1071-86
references: 12486108
references: Nat Cell Biol. 2009 Dec;11(12):1438-43
references: 19915557
references: Cell Motil Cytoskeleton. 1996;33(4):241-51
references: 8801030
references: Nature. 2011 Jun 08;474(7350):179-83
references: 21654799
references: Mol Biol Cell. 2011 Feb 1;22(3):327-41
references: 21148292
references: Biophys J. 1999 Oct;77(4):1992-2002
references: 10512819
references: J Cell Biol. 2005 May 9;169(3):515-26
references: 15866889
references: Proc Natl Acad Sci U S A. 1988 Aug;85(16):5946-50
references: 3413068
references: Proc Natl Acad Sci U S A. 1980 Nov;77(11):6639-43
references: 6935675
references: EMBO Rep. 2010 Oct;11(10):744-50
references: 20865016
references: Biophys J. 2008 Dec;95(11):5374-84
references: 18775961
references: J Cell Sci. 2011 Jun 1;124(Pt 11):1857-66
references: 21558415
references: Mol Biol Cell. 1999 Aug;10(8):2481-91
references: 10436006
references: Curr Opin Cell Biol. 2004 Feb;16(1):14-23
references: 15037300
references: J Cell Biol. 2003 Jan 20;160(2):267-77
references: 12527751
references: J Cell Sci. 2012 Jul 1;125(Pt 13):3051-60
references: 22797913
references: Neuron. 1988 Nov;1(9):761-72
references: 3078414
references: Nature. 2005 May 12;435(7039):191-4
references: 15889088
references: J Cell Sci. 2012 Jul 1;125(Pt 13):3025-38
references: 22797926
references: J Cell Sci. 2011 Apr 15;124(Pt 8):1256-67
references: 21444753
references: Science. 2004 Sep 17;305(5691):1782-6
references: 15375270
references: Annu Rev Cell Dev Biol. 2010;26:335-61
references: 19575667
references: Cell. 2006 Aug 25;126(4):677-89
references: 16923388
references: Oncogene. 2009 Apr 2;28(13):1570-83
references: 19234490
references: Curr Opin Cell Biol. 2009 Oct;21(5):636-44
references: 19523798
references: Science. 2003 Dec 5;302(5651):1704-9
references: 14657486
references: J Cell Biol. 2012 Apr 2;197(1):105-14
references: 22472441
references: Proc Natl Acad Sci U S A. 1982 Apr;79(8):2603-7
references: 7045867
references: J Cell Biol. 1998 Apr 20;141(2):539-51
references: 9548730
references: Proc Natl Acad Sci U S A. 1983 Mar;80(5):1367-71
references: 6298789
references: Cell. 2011 Jun 24;145(7):1012-22
references: 21703446
references: J Cell Biol. 2000 Aug 21;150(4):797-806
references: 10953004
references: J Cell Biol. 2009 Feb 23;184(4):481-90
references: 19221195
references: Curr Biol. 2006 Aug 8;16(15):1515-23
references: 16890527
references: Cell. 2012 Jan 20;148(1-2):175-88
references: 22265410
references: Cell Biochem Biophys. 2007;47(2):300-20
references: 17652777
references: J Cell Biol. 2007 Feb 26;176(5):573-80
references: 17312025
references: Mol Biol Cell. 2012 Jul;23(13):2583-92
references: 22593214
references: Cell. 1996 Feb 9;84(3):359-69
references: 8608589
references: J Cell Biol. 2010 Jan 11;188(1):11-9
references: 19951899
references: J Cell Sci. 2012 Apr 1;125(Pt 7):1814-26
references: 22328516
references: Nat Cell Biol. 2005 Mar;7(3):255-61
references: 15723050
references: J Exp Zool. 1989 Aug;251(2):167-85
references: 2549171
references: Am J Physiol Cell Physiol. 2010 Mar;298(3):C749-63
references: 19940066
references: J Embryol Exp Morphol. 1970 Nov;24(3):625-40
references: 4923996
references: Nat Rev Mol Cell Biol. 2008 Sep;9(9):730-6
references: 18628785
references: Cell. 2004 Feb 6;116(3):431-43
references: 15016377
references: J Cell Sci. 2006 Dec 15;119(Pt 24):5204-14
references: 17158922
references: Small GTPases. 2012 Jan-Mar;3(1):45-52
references: 22714417
references: Cancer Cell. 2011 Aug 16;20(2):229-45
references: 21840487
references: J Cell Biol. 1982 Mar;92(3):747-52
references: 7085756
references: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13661-5
references: 9391082
references: J Cell Biol. 2003 Jan 20;160(2):255-65
references: 12538643
references: Cell Cycle. 2009 May 15;8(10):1484-7
references: 19372747
references: Mol Biol Cell. 2012 Dec;23(24):4739-50
references: 23097497
references: J Cell Biol. 2002 Jul 8;158(1):153-64
references: 12105187
references: Exp Cell Res. 2012 Apr 1;318(6):741-52
references: 22233682
references: Science. 2007 Jan 5;315(5808):111-5
references: 17204653
references: Nat Cell Biol. 2007 Oct;9(10):1110-21
references: 17909522
references: Annu Rev Cell Dev Biol. 2011;27:185-211
references: 21801014
references: Dev Biol. 1973 Jan;30(1):69-103
references: 4735370
references: J Cell Biol. 2007 May 7;177(3):527-38
references: 17485492
references: J Cell Biol. 1986 Aug;103(2):605-12
references: 3733883
references: Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10889-94
references: 16832052
references: Nat Cell Biol. 2003 Aug;5(8):711-9
references: 12844144
references: Trends Cell Biol. 2011 Dec;21(12):718-26
references: 21924908
references: Nature. 2009 Sep 3;461(7260):99-103
references: 19693013
references: Cell. 2008 Oct 31;135(3):510-23
references: 18984162
references: Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14434-9
references: 22786929
references: Nat Cell Biol. 2008 Sep;10(9):1039-50
references: 19160484
references: Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16245-50
references: 19805288
references: J Cell Biol. 1975 Nov;67(2PT.1):400-18
references: 1194354