Skip to main content
PMC home page
Molecular Biology of the Cell logoLink to Molecular Biology of the Cell
. 1994 Apr;5(4):389–393. doi: 10.1091/mbc.5.4.389

Integrating with integrins.

M A Schwartz 1, D E Ingber 1
PMCID: PMC301049  PMID: 8054683

Abstract

Our central claim is that signaling by integrins provides a mechanism by which signals generated in response to adhesion, soluble hormones, and mechanical forces can interact. Such interactions permit cells to integrate these different classes of external stimuli and hence to orchestrate an efficient response. This integrating function of integrins is likely to be essential for much of development and physiology, as well as complex pathologies such as cancer. Understanding in detail how these signals are transduced and processed is likely to be an important area of research in the near future.

Full text

PDF
389

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albelda S. M., Mette S. A., Elder D. E., Stewart R., Damjanovich L., Herlyn M., Buck C. A. Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. Cancer Res. 1990 Oct 15;50(20):6757–6764. [PubMed] [Google Scholar]
  2. Bishop J. M. Molecular themes in oncogenesis. Cell. 1991 Jan 25;64(2):235–248. doi: 10.1016/0092-8674(91)90636-d. [DOI] [PubMed] [Google Scholar]
  3. Burridge K., Fath K., Kelly T., Nuckolls G., Turner C. Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. Annu Rev Cell Biol. 1988;4:487–525. doi: 10.1146/annurev.cb.04.110188.002415. [DOI] [PubMed] [Google Scholar]
  4. Carter D. R., Orr T. E., Fyhrie D. P. Relationships between loading history and femoral cancellous bone architecture. J Biomech. 1989;22(3):231–244. doi: 10.1016/0021-9290(89)90091-2. [DOI] [PubMed] [Google Scholar]
  5. Chan B. M., Matsuura N., Takada Y., Zetter B. R., Hemler M. E. In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells. Science. 1991 Mar 29;251(5001):1600–1602. doi: 10.1126/science.2011740. [DOI] [PubMed] [Google Scholar]
  6. Damsky C. H., Werb Z. Signal transduction by integrin receptors for extracellular matrix: cooperative processing of extracellular information. Curr Opin Cell Biol. 1992 Oct;4(5):772–781. doi: 10.1016/0955-0674(92)90100-q. [DOI] [PubMed] [Google Scholar]
  7. Danowski B. A., Harris A. K. Changes in fibroblast contractility, morphology, and adhesion in response to a phorbol ester tumor promoter. Exp Cell Res. 1988 Jul;177(1):47–59. doi: 10.1016/0014-4827(88)90024-9. [DOI] [PubMed] [Google Scholar]
  8. Danø K., Andreasen P. A., Grøndahl-Hansen J., Kristensen P., Nielsen L. S., Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res. 1985;44:139–266. doi: 10.1016/s0065-230x(08)60028-7. [DOI] [PubMed] [Google Scholar]
  9. Davies P. F., Tripathi S. C. Mechanical stress mechanisms and the cell. An endothelial paradigm. Circ Res. 1993 Feb;72(2):239–245. doi: 10.1161/01.res.72.2.239. [DOI] [PubMed] [Google Scholar]
  10. Duke P. J., Durnova G., Montufar-Solis D. Histomorphometric and electron microscopic analyses of tibial epiphyseal plates from Cosmos 1887 rats. FASEB J. 1990 Jan;4(1):41–46. doi: 10.1096/fasebj.4.1.2295377. [DOI] [PubMed] [Google Scholar]
  11. Emerman J. T., Pitelka D. R. Maintenance and induction of morphological differentiation in dissociated mammary epithelium on floating collagen membranes. In Vitro. 1977 May;13(5):316–328. doi: 10.1007/BF02616178. [DOI] [PubMed] [Google Scholar]
  12. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  13. Felding-Habermann B., Mueller B. M., Romerdahl C. A., Cheresh D. A. Involvement of integrin alpha V gene expression in human melanoma tumorigenicity. J Clin Invest. 1992 Jun;89(6):2018–2022. doi: 10.1172/JCI115811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fuortes M., Jin W. W., Nathan C. Adhesion-dependent protein tyrosine phosphorylation in neutrophils treated with tumor necrosis factor. J Cell Biol. 1993 Feb;120(3):777–784. doi: 10.1083/jcb.120.3.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Giancotti F. G., Ruoslahti E. Elevated levels of the alpha 5 beta 1 fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cells. Cell. 1990 Mar 9;60(5):849–859. doi: 10.1016/0092-8674(90)90098-y. [DOI] [PubMed] [Google Scholar]
  16. Glück U., Kwiatkowski D. J., Ben-Ze'ev A. Suppression of tumorigenicity in simian virus 40-transformed 3T3 cells transfected with alpha-actinin cDNA. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):383–387. doi: 10.1073/pnas.90.2.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Guadagno T. M., Ohtsubo M., Roberts J. M., Assoian R. K. A link between cyclin A expression and adhesion-dependent cell cycle progression. Science. 1993 Dec 3;262(5139):1572–1575. doi: 10.1126/science.8248807. [DOI] [PubMed] [Google Scholar]
  18. Guan J. L., Shalloway D. Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature. 1992 Aug 20;358(6388):690–692. doi: 10.1038/358690a0. [DOI] [PubMed] [Google Scholar]
  19. Hamawy M. M., Mergenhagen S. E., Siraganian R. P. Cell adherence to fibronectin and the aggregation of the high affinity immunoglobulin E receptor synergistically regulate tyrosine phosphorylation of 105-115-kDa proteins. J Biol Chem. 1993 Mar 5;268(7):5227–5233. [PubMed] [Google Scholar]
  20. Hedrick L., Cho K. R., Vogelstein B. Cell adhesion molecules as tumour suppressors. Trends Cell Biol. 1993 Feb;3(2):36–39. doi: 10.1016/0962-8924(93)90148-t. [DOI] [PubMed] [Google Scholar]
  21. Heimark R. L., Twardzik D. R., Schwartz S. M. Inhibition of endothelial regeneration by type-beta transforming growth factor from platelets. Science. 1986 Sep 5;233(4768):1078–1080. doi: 10.1126/science.3461562. [DOI] [PubMed] [Google Scholar]
  22. Ingber D. E., Folkman J. Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: role of extracellular matrix. J Cell Biol. 1989 Jul;109(1):317–330. doi: 10.1083/jcb.109.1.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ingber D. E., Madri J. A., Jamieson J. D. Role of basal lamina in neoplastic disorganization of tissue architecture. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3901–3905. doi: 10.1073/pnas.78.6.3901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ingber D. E., Prusty D., Frangioni J. V., Cragoe E. J., Jr, Lechene C., Schwartz M. A. Control of intracellular pH and growth by fibronectin in capillary endothelial cells. J Cell Biol. 1990 May;110(5):1803–1811. doi: 10.1083/jcb.110.5.1803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ingber D., Folkman J. Inhibition of angiogenesis through modulation of collagen metabolism. Lab Invest. 1988 Jul;59(1):44–51. [PubMed] [Google Scholar]
  26. Ingber D. Integrins as mechanochemical transducers. Curr Opin Cell Biol. 1991 Oct;3(5):841–848. doi: 10.1016/0955-0674(91)90058-7. [DOI] [PubMed] [Google Scholar]
  27. Levesque M. J., Nerem R. M., Sprague E. A. Vascular endothelial cell proliferation in culture and the influence of flow. Biomaterials. 1990 Nov;11(9):702–707. doi: 10.1016/0142-9612(90)90031-k. [DOI] [PubMed] [Google Scholar]
  28. Massagué J. The transforming growth factor-beta family. Annu Rev Cell Biol. 1990;6:597–641. doi: 10.1146/annurev.cb.06.110190.003121. [DOI] [PubMed] [Google Scholar]
  29. McNamee H. P., Ingber D. E., Schwartz M. A. Adhesion to fibronectin stimulates inositol lipid synthesis and enhances PDGF-induced inositol lipid breakdown. J Cell Biol. 1993 May;121(3):673–678. doi: 10.1083/jcb.121.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Meredith J. E., Jr, Fazeli B., Schwartz M. A. The extracellular matrix as a cell survival factor. Mol Biol Cell. 1993 Sep;4(9):953–961. doi: 10.1091/mbc.4.9.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mooney D., Hansen L., Vacanti J., Langer R., Farmer S., Ingber D. Switching from differentiation to growth in hepatocytes: control by extracellular matrix. J Cell Physiol. 1992 Jun;151(3):497–505. doi: 10.1002/jcp.1041510308. [DOI] [PubMed] [Google Scholar]
  32. Opas M. Expression of the differentiated phenotype by epithelial cells in vitro is regulated by both biochemistry and mechanics of the substratum. Dev Biol. 1989 Feb;131(2):281–293. doi: 10.1016/s0012-1606(89)80001-6. [DOI] [PubMed] [Google Scholar]
  33. Plantefaber L. C., Hynes R. O. Changes in integrin receptors on oncogenically transformed cells. Cell. 1989 Jan 27;56(2):281–290. doi: 10.1016/0092-8674(89)90902-1. [DOI] [PubMed] [Google Scholar]
  34. Rodríguez Fernández J. L., Geiger B., Salomon D., Ben-Ze'ev A. Overexpression of vinculin suppresses cell motility in BALB/c 3T3 cells. Cell Motil Cytoskeleton. 1992;22(2):127–134. doi: 10.1002/cm.970220206. [DOI] [PubMed] [Google Scholar]
  35. Schiro J. A., Chan B. M., Roswit W. T., Kassner P. D., Pentland A. P., Hemler M. E., Eisen A. Z., Kupper T. S. Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells. Cell. 1991 Oct 18;67(2):403–410. doi: 10.1016/0092-8674(91)90191-z. [DOI] [PubMed] [Google Scholar]
  36. Schmidt C. E., Horwitz A. F., Lauffenburger D. A., Sheetz M. P. Integrin-cytoskeletal interactions in migrating fibroblasts are dynamic, asymmetric, and regulated. J Cell Biol. 1993 Nov;123(4):977–991. doi: 10.1083/jcb.123.4.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schwartz M. A., Lechene C. Adhesion is required for protein kinase C-dependent activation of the Na+/H+ antiporter by platelet-derived growth factor. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6138–6141. doi: 10.1073/pnas.89.13.6138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Schwartz M. A., Rupp E. E., Frangioni J. V., Lechene C. P. Cytoplasmic pH and anchorage-independent growth induced by v-Ki-ras, v-src or polyoma middle T. Oncogene. 1990 Jan;5(1):55–58. [PubMed] [Google Scholar]
  39. Schwartz M. A. Transmembrane signalling by integrins. Trends Cell Biol. 1992 Oct;2(10):304–308. doi: 10.1016/0962-8924(92)90120-c. [DOI] [PubMed] [Google Scholar]
  40. Symington B. E. Fibronectin receptor overexpression and loss of transformed phenotype in a stable variant of the K562 cell line. Cell Regul. 1990 Aug;1(9):637–648. doi: 10.1091/mbc.1.9.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Südhof T. C., De Camilli P., Niemann H., Jahn R. Membrane fusion machinery: insights from synaptic proteins. Cell. 1993 Oct 8;75(1):1–4. [PubMed] [Google Scholar]
  42. Takeichi M. Cadherins in cancer: implications for invasion and metastasis. Curr Opin Cell Biol. 1993 Oct;5(5):806–811. doi: 10.1016/0955-0674(93)90029-p. [DOI] [PubMed] [Google Scholar]
  43. Talhouk R. S., Bissell M. J., Werb Z. Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J Cell Biol. 1992 Sep;118(5):1271–1282. doi: 10.1083/jcb.118.5.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Tolsma S. S., Volpert O. V., Good D. J., Frazier W. A., Polverini P. J., Bouck N. Peptides derived from two separate domains of the matrix protein thrombospondin-1 have anti-angiogenic activity. J Cell Biol. 1993 Jul;122(2):497–511. doi: 10.1083/jcb.122.2.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tucker R. W., Butterfield C. E., Folkman J. Interaction of serum and cell spreading affects the growth of neoplastic and non-neoplastic fibroblasts. J Supramol Struct Cell Biochem. 1981;15(1):29–40. doi: 10.1002/jsscb.1981.380150104. [DOI] [PubMed] [Google Scholar]
  46. Vandenburgh H. H., Swasdison S., Karlisch P. Computer-aided mechanogenesis of skeletal muscle organs from single cells in vitro. FASEB J. 1991 Oct;5(13):2860–2867. doi: 10.1096/fasebj.5.13.1916108. [DOI] [PubMed] [Google Scholar]
  47. Wang N., Butler J. P., Ingber D. E. Mechanotransduction across the cell surface and through the cytoskeleton. Science. 1993 May 21;260(5111):1124–1127. doi: 10.1126/science.7684161. [DOI] [PubMed] [Google Scholar]
  48. Watanabe T. K., Hansen L. J., Reddy N. K., Kanwar Y. S., Reddy J. K. Differentiation of pancreatic acinar carcinoma cells cultured on rat testicular seminiferous tubular basement membranes. Cancer Res. 1984 Nov;44(11):5361–5368. [PubMed] [Google Scholar]
  49. Wittelsberger S. C., Kleene K., Penman S. Progressive loss of shape-responsive metabolic controls in cells with increasingly transformed phenotype. Cell. 1981 Jun;24(3):859–866. doi: 10.1016/0092-8674(81)90111-2. [DOI] [PubMed] [Google Scholar]

Articles from Molecular Biology of the Cell are provided here courtesy of American Society for Cell Biology

RESOURCES