Caldesmon-dependent switching between capillary endothelial cell growth and apoptosis through modulation of cell shape and contractility Article DOI:
Cite this article as: Numaguchi, Y., Huang, S., Polte, T.R. et al. Angiogenesis (2003) 6: 55. doi:10.1023/A:1025821517679 Abstract
Caldesmon (CaD), a protein component of the actomyosin filament apparatus, modulates cell shape and cytoskeletal structure when overexpressed. When capillary endothelial cells were infected with an adenoviral vector encoding GFP-CaD under Tet-Off control, progressive inhibition of contractility, loss of actin stress fibers, disassembly of focal adhesions, and cell retraction resulted. This was accompanied by a cell shape (rounding)-dependent increase in apoptosis and concomitant inhibition of cell cycle progression. Cell growth also was inhibited in low expressor cells in which cell tension was suppressed independently of significant changes in cell shape, cytoskeletal structure, or focal adhesions. Thus, changes in both cytoskeletal structure and contractility appear to be central to the mechanism by which extracellular matrix-dependent changes in capillary cell shape influence growth and apoptosis during angiogenesis, and hence the cytoskeleton may represent a potential target for anti-angiogenesis therapy.
cell cycle cytoskeleton extracellular matrix mechanical force microfilament tension References
Ingber DE. Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. Circ Res 2002; 91: 877–87.
Ingber DE, Madri JA, Folkman J. A possible mechanism for inhibition of angiogenesis by angiostatic steroids: Induction of capillary basement membrane dissolution. Endocrinology 1986; 119: 1768–75.
Ingber DE, Folkman J. How does extracellular matrix control capillary morphogenesis? Cell 1989; 58: 803–5.
Singhvi R, Kumar A, Lopez GP et al. Engineering cell shape and function. Science 1994; 264: 696–8.
Chen CS, Mrksich M, Huang S et al. Geometric control of cell life and death. Science 1997; 276: 1425–8.
Huang S, Chen CS, Ingber DE. Control of Cyclin D1, p27
, and cell cycle progression in human capillary endothelial cells by cell shape and cytoskeletal tension. Mol Biol Cell 1998; 9: 3179–293.
Parker KK, Brock AL, Brangwynne C et al. Directional control of lamellipodia extension by constructing cell shape and orienting cell tractional forces. FASEB J 2002; 16: 1195–204.
Flusberg DA, Numaguchi Y, Ingber DE. Cooperative control of Akt phopsphorylation, bcl-2 expression, and apoptosis by cytoskeletal microfilaments and microtubules in capillary endothelial cells. Mol Biol Cell 2001; 12: 3087–94.
Ingber DE, Folkman J. Inhibition of angiogenesis through inhibition of collagen metabolism. Lab Invest 1988; 59: 44–51.
Iwig M, Glaesser D, Bethge M. Cell shape-mediated growth control of lens epithelial cells grown in culture. Exp Cell Res 1981; 131: 47–55.
Sauman I, Berry SJ. Cytochalasin D treatment triggers premature apoptosis of insect ovarian follicle and nurse cells. Int J Dev Biol 1993; 37: 441–50.
Böhmer RM, Scharf E, Assoian RK. Cytoskeletal integrity is required throughout the mitogen stimulation phase of the cell cycle and mediates the anchorage-dependent expression of cyclin D1. Mol Biol Cell 1996; 7: 101–11.
Korichneva I, Hammerling U. F-actin as a functional target for retro-retinoids: A potential role in anhydroretinol-triggered cell death. J Cell Sci 1999; 112: 2521–8.
Huang S, Ingber DE. A discrete cell cycle checkpoint late G1 that is cytoskeleton-dependent and MAP kinase (Erk)-independent. Exp Cell Res 2002; 275: 255–64.
Helfman DM, Levy ET, Berthier C et al. Caldesmon inhibits nonmuscle cell contractility and interferes with the formation of focal adhesions. Mol Biol Cell 1999; 10: 3097–112.
Geiger B, Bershadsky A. Assembly and mechanosensory function of focal contacts. Curr Opin Cell Biol 2001; 5: 584–92.
Sobue K, Muramoto Y, Fujita M, Kakiuchi S. Purification of a calmodulin-binding protein from chicken gizzard that interacts with F-actin. Proc Natl Acad Sci USA 1981; 78: 5652–5.
Matsumura F, Yamashiro S. Caldesmon. Curr Opin Cell Biol 1993; 5: 70–6.
Huber PA. Caldesmon. Int J Biochem Cell Biol 1997; 29: 1047–51.
Marston SB, Fraser IDC, Huber PAJ et al. Location of two contact sites between human smooth muscle caldesmon and Ca
-calmodulin. J Biol Chem 1994; 269: 8134–9.
Chalovich JM, Sen A, Resetar A et al. Caldesmon: binding to actin and myosin and effects on elementary steps in the ATPase cycle. Acta Physiol Scand 1998; 164: 427–35.
Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA 1992; 89: 5547–51.
Gossen M, Freundlieb S, BenderGet al. Transcriptional activation by tetracyclines in mammalian cells. Science 1995; 268: 1766–9.
Dike LE, Ingber DE. Integrin-dependent induction of early growth response genes in capillary endothelial cells. J Cell Sci 1996; 109: 2855–63.
Tolic-Norrelykke IM, Butler JP, Chen J, Wang N. Spatial and temporal traction response in human airway smooth muscle cells. Am J Physiol Cell Physiol 2002; 283: C1254–66.
Ingber DE, Prusty D, Sun Z et al. Cell shape, cytoskeletal mechanics, and cell cycle control in angiogenesis. J Biomech 1995; 28: 1471–84.
Pawlak G, Helfman DM. Cytoskeletal changes in cell transformation and tumorgenesis. Curr Opin Gen Dev 2001; 11: 41–7.
Pelham RJ Jr, Wang Y. High resolution detection of mechanical forces exerted by locomoting fibroblasts on the substrate. Mol Biol Cell 1999; 10: 935–45.
Wang N, Naruse K, Stamenovic D et al. Mechanical behavior of living cells consistent with the tensegrity model. Proc Natl Acad Sci USA 2001; 98: 7765–70.
Rubtsova SN, Kondratov RV, Kopnin PB et al. Disruption of actin microfilaments by cytochalasin D leads to activation of p53. FEBS Lett 1998; 430: 353–7.
Ingber DE. Cellular tensegrity: Defining new rules of biological design that govern the cytoskeleton. J Cell Sci 1993; 104: 613–27.
Wang N, Ingber DE. Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. Biophys J 1994; 66: 1281–9.
Wang N, Ostuni E, Whitesides GM, Ingber DE. Micropatterning traction forces in living cells. Cell Motil Cytoskeleton 2002; 52: 97–106.
Wang N, Tolic-Norrelykke IM, Chen J et al. Cell prestress. I. Stiffness and pretress are closely associated in adherent contractile cells. Am J Physiol Cell Physiol 2003; 282: C606–16.
Wang N, Butler JP, Ingber DE. Mechanotransduction across the cell surface and through the cytoskeleton. Science 1993; 260: 1124–7.
Maniotis A, Chen C, Ingber DE. Demonstration of mechanical connections between integrins, cytoskeletal filaments and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci USA 1997; 94: 849–54.
Choquet D, Felsenfeld DP, Sheetz MP. Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages. Cell 1997; 88: 39–48.
Chrzanowska-Wodnicka M, Burridge K. Focal adhesions, contractility and signaling. Annu Rev Cell Dev Biol 1996; 12: 463–518.
Balaban NQ, Shwarz US, Riveline D et al. Force and focal adhesion assembly: A close relationship studied using elastic micropatterned substrates. Nat Cell Biol 2001; 3: 466–72.
Riveline D, Zamir E, Balaban NQ et al. Focal contacts as mechanosensors: Externally applied local mechanical force induces growth of focal contacts by an mDia1–dependent and ROCKindependent mechanism. J Cell Biol 2001; 153: 1175–86.
Folkman J, Moscona A. Role of cell shape in growth control. Nature 1978; 273: 345–9.
Adam LP, Hathaway DR. Identification of mitogen-activated protein kinase phosphorylation sequences in mammalian h-caldesmon. FEBS Lett 1993; 322: 56–60.
Huang S, Ingber DE. The structual control mechanical complexity of cell-growth control. Nat Cell Biol 1999; 1: E131–8.
Korff T, Augustin HG. Tensional forces in fibrillar extracellular matrices control directional capillary sprouting. J Cell Sci 1999; 112: 3249–58.
Grove AD, Prabhu VV, Young BL et al. Both protein activation and gene expression are involved in early vascular tube formation
. Clin Cancer Res 2002; 8: 3019–26.
Roskelley CD, Srebrow A, Bissell MJ. A hierarchy of ECMmediated signalling regulates tissue-specific gene expression. Curr Opin Cell Biol 1995; 7: 736–47.
Boudreau N, Werb Z, Bissell MJ. Suppression of apoptosis by basement membrane requires three-dimensional tissue organization and withdrawal from the cell cycle. Proc Natl Acad Sci USA 1996; 93: 3509–13.
Weaver VM, Lelievre S, Lakins JN et al. Beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell 2002; 2: 205–16.
Moore KA, Huang S, Kong Y et al. Control of embryonic lung branching morphogenesis by the Rho activator, cytotoxic necrotizing factor 1. J Surg Res 2002; 104: 95–100.
Harding TC, Geddes BJ, Murphy D et al. Switching transgene expression in the brain using an adenoviral tetracycline-regulatable system. Nat Biotech 1998; 18: 553–5.
Google Scholar Copyright information
© Kluwer Academic Publishers 2003