ROCK-generated Contractility Regulates Breast Epithelial Cell Differentiation in Response to the Physical Properties of a Three-dimensional Collagen Matrix

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2003 Nov 12

PMID 14610060

Citations 257

Authors

Michele A Wozniak

Radhika Desai

Patricia A Solski

Channing J Der

Patricia J Keely

Affiliations

Soon will be listed here.

Abstract

Breast epithelial cells differentiate into tubules when cultured in floating three-dimensional (3D) collagen gels, but not when the cells are cultured in the same collagen matrix that is attached to the culture dish. These observations suggest that the biophysical properties of collagenous matrices regulate epithelial differentiation, but the mechanism by which this occurs is unknown. Tubulogenesis required the contraction of floating collagen gels through Rho and ROCK-mediated contractility. ROCK-mediated contractility diminished Rho activity in a floating 3D collagen gel, and corresponded to a loss of FAK phosphorylated at Y397 localized to 3D matrix adhesions. Increasing the density of floating 3D collagen gels also disrupted tubulogenesis, promoted FAK phosphorylation, and sustained high Rho activity. These data demonstrate the novel finding that breast epithelial cells sense the rigidity or density of their environment via ROCK-mediated contractility and a subsequent down-regulation of Rho and FAK function, which is necessary for breast epithelial tubulogenesis to occur.

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References

Blanchoin L, Amann K, Higgs H, Marchand J, Kaiser D, Pollard T . Direct observation of dendritic actin filament networks nucleated by Arp2/3 complex and WASP/Scar proteins. Nature. 2000; 404(6781):1007-11. DOI: 10.1038/35010008. View

Yano Y, Geibel J, Sumpio B . Tyrosine phosphorylation of pp125FAK and paxillin in aortic endothelial cells induced by mechanical strain. Am J Physiol. 1996; 271(2 Pt 1):C635-49. DOI: 10.1152/ajpcell.1996.271.2.C635. View

Chakravarty G, Roy D, Gonzales M, Gay J, Contreras A, Rosen J . P190-B, a Rho-GTPase-activating protein, is differentially expressed in terminal end buds and breast cancer. Cell Growth Differ. 2000; 11(7):343-54. View

Totsukawa G, Yamakita Y, Yamashiro S, Hartshorne D, Sasaki Y, Matsumura F . Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts. J Cell Biol. 2000; 150(4):797-806. PMC: 2175273. DOI: 10.1083/jcb.150.4.797. View

Han D, Shen T, Guan J . Role of Grb7 targeting to focal contacts and its phosphorylation by focal adhesion kinase in regulation of cell migration. J Biol Chem. 2000; 275(37):28911-7. DOI: 10.1074/jbc.M001997200. View

Ren X, Kiosses W, Sieg D, Otey C, Schlaepfer D, Schwartz M . Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. J Cell Sci. 2000; 113 ( Pt 20):3673-8. DOI: 10.1242/jcs.113.20.3673. View

Clark E, King W, Brugge J, Symons M, Hynes R . Integrin-mediated signals regulated by members of the rho family of GTPases. J Cell Biol. 1998; 142(2):573-86. PMC: 2133065. DOI: 10.1083/jcb.142.2.573. View

Boyd N, Lockwood G, Byng J, Tritchler D, Yaffe M . Mammographic densities and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1998; 7(12):1133-44. View

Zhao J, Reiske H, Guan J . Regulation of the cell cycle by focal adhesion kinase. J Cell Biol. 1998; 143(7):1997-2008. PMC: 2175220. DOI: 10.1083/jcb.143.7.1997. View

10.

Tang D, Mehta D, Gunst S . Mechanosensitive tyrosine phosphorylation of paxillin and focal adhesion kinase in tracheal smooth muscle. Am J Physiol. 1999; 276(1):C250-8. DOI: 10.1152/ajpcell.1999.276.1.C250. View

11.

Ren X, Kiosses W, Schwartz M . Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton. EMBO J. 1999; 18(3):578-85. PMC: 1171150. DOI: 10.1093/emboj/18.3.578. View

12.

Svitkina T, Borisy G . Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia. J Cell Biol. 1999; 145(5):1009-26. PMC: 2133125. DOI: 10.1083/jcb.145.5.1009. View

13.

Zutter M, Santoro S, Wu J, Wakatsuki T, Dickeson S, Elson E . Collagen receptor control of epithelial morphogenesis and cell cycle progression. Am J Pathol. 1999; 155(3):927-40. PMC: 1866884. DOI: 10.1016/S0002-9440(10)65192-9. View

14.

Guo Y, Martin L, Hanna W, Banerjee D, Miller N, Fishell E . Growth factors and stromal matrix proteins associated with mammographic densities. Cancer Epidemiol Biomarkers Prev. 2001; 10(3):243-8. View

15.

Balaban N, Schwarz U, Riveline D, Goichberg P, Tzur G, Sabanay I . Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat Cell Biol. 2001; 3(5):466-72. DOI: 10.1038/35074532. View

16.

Riveline D, Zamir E, Balaban N, Schwarz U, Ishizaki T, Narumiya S . Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J Cell Biol. 2001; 153(6):1175-86. PMC: 2192034. DOI: 10.1083/jcb.153.6.1175. View

17.

Wang H, Dembo M, Hanks S, Wang Y . Focal adhesion kinase is involved in mechanosensing during fibroblast migration. Proc Natl Acad Sci U S A. 2001; 98(20):11295-300. PMC: 58723. DOI: 10.1073/pnas.201201198. View

18.

Schwartz M, Assoian R . Integrins and cell proliferation: regulation of cyclin-dependent kinases via cytoplasmic signaling pathways. J Cell Sci. 2001; 114(Pt 14):2553-60. DOI: 10.1242/jcs.114.14.2553. View

19.

Cukierman E, Pankov R, Stevens D, Yamada K . Taking cell-matrix adhesions to the third dimension. Science. 2001; 294(5547):1708-12. DOI: 10.1126/science.1064829. View

20.

Koo L, Irvine D, Mayes A, Lauffenburger D, Griffith L . Co-regulation of cell adhesion by nanoscale RGD organization and mechanical stimulus. J Cell Sci. 2002; 115(Pt 7):1423-33. DOI: 10.1242/jcs.115.7.1423. View