Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

p27 is involved in N-cadherin-mediated contact inhibition of cell growth and S-phase entry

Oncogene volume 18, pages 869–876 (1999)Cite this article

Abstract

In this study the direct involvement of cadherins in adhesion-mediated growth inhibition was investigated. It is shown here that overexpression of N-cadherin in CHO cells significantly suppresses their growth rate. Interaction of these cells and two additional fibroblastic lines with synthetic beads coated with N-cadherin ligands (recombinant N-cadherin ectodomain or specific antibodies) leads to growth arrest at the G1 phase of the cell cycle. The cadherin-reactive beads inhibit the entry into S phase and the reduction in the levels of cyclin-dependent kinase (cdk) inhibitors p21 and p27, following serum-stimulation of starved cells. In exponentially growing cells these beads induce G1 arrest accompanied by elevation in p27 only. We propose that cadherin-mediated signaling is involved in contact inhibition of growth by inducing cell cycle arrest at the G1 phase and elevation of p27 levels.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 5
Figure 2
Figure 3
Figure 4
Figure 6

Similar content being viewed by others

References

  • Becker KF, Atkinson MJ, Reich U, Becker I, Nekarda H, Siewert JR and Hofler H. . 1994 Cancer Res. 54: 3845–3852.

  • Caveda L, Martin-Padura I, Navarro P, Breviario F, Corada M, Gulino D, Lampugnani MG and Dejana E. . 1996 J. Clin. Invest. 98: 886–893.

  • Chen H, Hughes DD, Chain TA, Sedat JW and Agard DA. . 1996 J. Struct. Biol. 116: 56–60.

  • Coats S, Flanagan M, Nourse J and Roberts J. . 1996 Science 272: 877–880.

  • Deleu L, Fuks F, Spitkovsky D, Horlein R, Faisst S and Rommelaere J. . 1998 Mol. Cell. Biol. 18: 409–419.

  • Dietrich C, Wallenfang K, Oesch F and Wieser R. . 1997 Oncogene 15: 2743–2747.

  • Fagotto F, Funayama N, Gluck U and Gumbiner BM. . 1996 J. Cell. Biol. 132: 1105–1114.

  • Hengst L and Reed S. . 1996 Science 271: 1861–1864.

  • Holley RW. . 1975 Nature 258: 487–490.

  • Huber O, Bierkamp C and Kemler R. . 1996 Curr. Opin. Cell Biol. 8: 685–691.

  • Huttenlocher A, Lakonishok M, Kinder M, Wu S, Truong T, Knudson KA and Horwitz AF. . 1998 JCB 141: 515–526.

  • Johnson M, Dimitrov D, Vojta PJ, Barrett JC, Noda A, Pereira-Smith OM and Smith JR. . 1994 Mol. Carcinog. 11: 59–64.

  • Kam Z, Jones MO, Chen H, Agard DA and Sedat JW. . 1993 Bioimaging 1: 71–81.

  • Kandikonda S, Oda D, Niederman R and Sorkin B. . 1996 Cell Adhes. Comm. 4: 13–24.

  • Kato A, Takahashi H, Takahashi Y and Matsushime H. . 1997 J. Biol. Chem. 272: 8065–8070.

  • Kato JY, Matsuka M, Polyak K, Massague J and Sherr C. . 1994 Cell 79: 487–496.

  • Levenberg S, Katz BZ, Yamada KM and Geiger B. . 1998a J. Cell. Sci. 111: 347–357.

  • Levenberg S, Sadot E, Goichberg P and Geiger B. . 1998b Cell Adhe. Commun. In press.

  • Millard S, Yani JS, Nguyen H, Pagano M, Kiyokawa H and Koff A. . 1997 J. Biol. Chem. 272: 7039–7098.

  • Miller JR and Moon RT. . 1996 Genes Dev. 10: 2527–2593.

  • Pagano M, Tam SW, Theodoras AM, Beer-Romero P, Del Sal G, Chau V, Yew PR, Dretta GF and Rolf M. . 1995 Science 269: 682–685.

  • Peifer M. . 1997 Science 275: 1752–1753.

  • Polyak K, Kato J, Solomon MJ, Sherr CJ, Massague J, Roberts JM and Koff A. . 1994a Genes & Develop. 8: 9–22.

  • Polyak K, Lee MH, Erdjument-Bromage H, Koff A, Roberts JM, Tempst P and Massague J. . 1994b Cell 78: 59–66.

  • Sanson B, White P and Vincent JP. . 1996 Nature 383: 627–630.

  • Tsukita S, Itoh M, Nagafuchi A, Yonemura S and Tsukita S. . 1993 J. Cell. Biol. 123: 1049–1053.

  • van de Wetering M, Cavallo R, Dooijes D, van Beest M, van Es J, Loureiro J, Ypma A, Hursh D, Jones T and Bejsovec A. . 1997 Cell 88: 789–799.

  • Volk T and Geiger B. . 1986 J. Cell Biol. 103: 1451–1464.

  • Weiser RJ, Heck R and Oesch F. . 1985 Exp. Cell Res. 158: 493–499.

  • Weiser RJ and Oesch F. . 1986 J. Cell Biol. 103: 361–367.

Download references

Acknowledgements

We would like to express our gratitude to Moshe Oren, Doron Ginsberg, Dalia Resnitzky and Ken Yamada for illuminating discussions and comments. This study was supported by the Israel Science Foundation and by the Rita Markus Foundation. BG holds the Erwin Neter Chair in Cell and Tumor Biology. ZK holds the Israel Pollak Chair of Biophysics.

Author information

Authors and Affiliations

  1. Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, 76100, Israel

    Shulamit Levenberg, Anat Yarden, Zvi Kam & Benjamin Geiger

Authors
  1. Shulamit Levenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anat Yarden
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zvi Kam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Benjamin Geiger
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Levenberg, S., Yarden, A., Kam, Z. et al. p27 is involved in N-cadherin-mediated contact inhibition of cell growth and S-phase entry. Oncogene 18, 869–876 (1999). https://doi.org/10.1038/sj.onc.1202396

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202396

Keywords

This article is cited by

Search

Advanced search

Quick links