Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel.
Cancer cells use different modes of migration, including integrin-dependent mesenchymal migration of elongated cells along elements of the 3D matrix as opposed to low-adhesion-, contraction-based amoeboid motility of rounded cells. We report that MDA-MB-231 human breast adenocarcinoma cells invade 3D Matrigel with a characteristic rounded morphology and with F-actin and myosin-IIa accumulating at the cell rear in a uropod-like structure. MDA-MB-231 cells display neither lamellipodia nor bleb extensions at the leading edge and do not require Arp2/3 complex activity for 3D invasion in Matrigel. Accumulation of phospho-MLC and blebbing activity were restricted to the uropod as reporters of actomyosin contractility, and velocimetric analysis of fluorescent beads embedded within the 3D matrix showed that pulling forces exerted to the matrix are restricted to the side and rear of cells. Inhibition of actomyosin contractility or β1 integrin function interferes with uropod formation, matrix deformation, and invasion through Matrigel. These findings support a model whereby actomyosin-based uropod contractility generates traction forces on the β1 integrin adhesion system to drive cell propulsion within the 3D matrix, with no contribution of lamellipodia extension or blebbing to movement.
Research Center, Institut Curie, F-75248 Paris, France.
Renaud
R
Poincloux
Olivier
O
Collin
Floria
F
Lizárraga
Maryse
M
Romao
Marcel
M
Debray
Matthieu
M
Piel
Philippe
P
Chavrier
D000230:Adenocarcinoma / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen; D004338:Drug Combinations; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D024462:Myosin Type II / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011509:Proteoglycans
D004338:Drug Combinations; D019012:Integrin beta1; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D024462:Myosin Type II
Nat Rev Mol Cell Biol. 2009 May;10(5):353-9
19373240
Chem Biol. 2009 Nov 25;16(11):1158-68
19942139
J Cell Biol. 2004 Nov 22;167(4):769-81
15557125
Biophys J. 2008 Oct;95(8):4077-88
18641063
J Cell Biol. 2009 Apr 6;185(1):11-9
19332889
J Cell Biol. 2005 Jan 31;168(3):441-52
15684033
Cell. 1996 Feb 9;84(3):359-69
8608589
Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18024-9
15601776
J Cell Biol. 2006 May 8;173(3):383-94
16651381
Cell. 2008 Oct 31;135(3):510-23
18984162
J Cell Biol. 2008 Jun 16;181(6):879-84
18541702
Science. 2008 Dec 12;322(5908):1705-10
19074353
Nat Rev Mol Cell Biol. 2009 Aug;10(8):538-49
19603038
Mol Biol Cell. 2007 Aug;18(8):3144-55
17567956
Matrix Biol. 2009 Jan;28(1):3-10
19010413
Science. 2001 Nov 23;294(5547):1708-12
11721053
Cancer Res. 2009 Apr 1;69(7):2792-800
19276357
Nat Rev Cancer. 2003 May;3(5):362-74
12724734
Curr Biol. 2008 Oct 14;18(19):1456-65
18835169
Dev Cell. 2006 Nov;11(5):613-27
17084355
Nat Rev Mol Cell Biol. 2009 Nov;10(11):778-90
19851336
Trends Cell Biol. 2008 Nov;18(11):560-74
18848450
Nat Cell Biol. 2007 Aug;9(8):893-904
17618273
Nat Med. 1999 Feb;5(2):221-5
9930872
J Cell Biol. 2003 Jan 20;160(2):267-77
12527751
Curr Opin Cell Biol. 2009 Oct;21(5):636-44
19523798
J Cell Sci. 2009 Sep 1;122(Pt 17):3015-24
19692588
J Cell Biol. 2009 Feb 23;184(4):481-90
19221195
Curr Biol. 2006 Aug 8;16(15):1515-23
16890527
Cell. 2006 Jun 30;125(7):1361-74
16814721
Nat Cell Biol. 2005 Mar;7(3):255-61
15723050
Nat Rev Mol Cell Biol. 2008 Sep;9(9):730-6
18628785
Mol Biol Cell. 2001 Dec;12(12):3947-54
11739792
Cell. 2007 Feb 9;128(3):561-75
17289574
Curr Opin Cell Biol. 2005 Oct;17(5):524-32
16112853
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18581-6
19846787
Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10889-94
16832052
Nat Cell Biol. 2003 Aug;5(8):711-9
12844144
Nat Methods. 2008 Jul;5(7):605-7
18536722