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:

Alpha-catenin is required for IGF-I-induced cellular migration but not invasion in human colonic cancer cells

Abstract

The mechanisms by which growth factors cooperate with cell adhesion molecules to modulate epithelial cell motility remain poorly understood. Here, we investigated the role of the E-cadherin/catenin complex in insulin-like growth factor (IGF-I)-dependent cell migration and invasion. We used variants of the HCT-8 colon cancer family that differ in their expression of αE-catenin, an intracellular molecule that links the E-cadherin/catenin complex to the actin cytoskeleton. Migration was determined using a monolayer wound model and cell invasion by the penetration of the cells into type-I collagen gels. We showed that α-catenin-deficient cells were not able to migrate in cohort upon IGF-I stimulation. Transfection of these cells with α-catenin isoforms (αN- or αT-catenin) restored migratory response IGF-I. These results suggest that α-catenins are involved in the signal issued from the E-cadherin/catenin complex to regulate IGF-I-stimulated migration. In contrast, IGF-I promoted invasion of both α-catenin-deficient and α-catenin-expressing cells, indicating that α-catenin did not participate in the regulation of IGF-I-induced invasion. Inhibition of E-cadherin function by treatment with MB-2 monoclonal antibodies inhibited both IGF-I-dependent cell migration and invasion. Taken together, our results indicate that functional α-catenin is essential for migration but not for invasion, while E-cadherin is involved in both phenomena.

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

Access options

Buy this article

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  • Andre F, Rigot V, Remacle-Bonnet M, Luis J, Pommier G and Marvaldi J . (1999a). Gastroenterology, 116, 64–77.

  • Andre F, Rigot V, Thimonier J, Montixi C, Parat F, Pommier G, Marvaldi J and Luis J . (1999b). Int. J. Cancer, 83, 497–505.

  • Angst BD, Marcozzi C and Magee AI . (2001). J. Cell Sci., 114, 629–641.

  • Barbier M, Attoub S, Calvez R, Laffargue M, Mareel M, Altruda F, Gespach C, Hirsch E and Wymann M . (2001). Nature, 413, 796.

  • Baserga R . (2000). Oncogene, 19, 5574–5581.

  • Behrens J, Vakaet L, Friis R, Winterhager E, Van Roy F, Mareel MM and Birchmeier W . (1993). J. Cell Biol., 120, 757–766.

  • Bracke ME, Vyncke BM, Bruyneel EA, Vermeulen SJ, De Bruyne GK, Van Larebeke NA, Vleminckx K, Van Roy FM and Mareel MM . (1993). Br. J. Cancer, 68, 282–289.

  • Conacci-Sorrell M, Zhurinsky J and Ben-Ze'ev A . (2002). J. Clin. Invest., 109, 987–991.

  • Debruyne P, Bruyneel E, Karaguni I-M, Li X, Flatau G, Müller O, Zimber A, Gespach C and Mareel M . (2002). Oncogene, 21, 7640–7650.

  • Furstenberger G and Senn HJ . (2002). Lancet Oncol., 3, 298–302.

  • Glukhova M, Koteliansky V, Sastre X and Thiery JP . (1995). Am. J. Pathol., 146, 706–716.

  • Guvakova MA and Surmacz E . (1999). Exp. Cell Res., 251, 244–255.

  • Hiscox S and Jiang WG . (1999). Biochem. Biophys. Res. Commun., 261, 406–411.

  • Janssens B, Goossens S, Staes K, Gilbert B, van Hengel J, Colpaert C, Bruyneel E, Mareel M and van Roy F . (2001). J. Cell Sci., 114, 3177–3188.

  • Jou TS and Nelson WJ . (1998). J. Cell Biol., 142, 85–100.

  • Kotelevets L, Noe V, Bruyneel E, Myssiakine E, Chastre E, Mareel M and Gespach C . (1998). J. Biol. Chem., 273, 14138–14145.

  • Leventhal P and Feldman E . (1997). Trends Endocrinol. Metab., 8, 1–6.

  • Mareel M and Leroy A . (2002). Physiol. Rev., 83, 337–376.

  • Matsubara S and Osawa M . (2001). J. Cell Biol., 154, 573–584.

  • Mauro L, Bartucci M, Morelli C, Ando S and Surmacz E . (2001). J. Biol. Chem., 276, 39892–39897.

  • Menke A, Philippi C, Vogelmann R, Seidel B, Lutz MP, Adler G and Wedlich D . (2001). Cancer Res., 61, 3508–3517.

  • Morali O, Delmas V, Moore R, Jeanney C, Thiery J and Larue L . (2001). Oncogene, 20, 4942–4950.

  • Nabeshima K, Inoue T, Shimao Y, Kataoka H and Koono M . (1999). Histol. Histopathol., 14, 1183–1197.

  • Sandhu M S, Dunger DB and Giovannucci EL . (2002). J. Natl. Cancer Inst., 94, 972–980.

  • Schwartz MA and Ginsberg MH . (2002). Nat. Cell Biol., 4, E65–E68.

  • Steelant W, Goeman J, Philippe J, Oomen L, Hilkens J, Krzewinski-Recchi M, Huet G, Van der Eycken J, Delannoy P, Bruyneel E and Mareel M . (2001). Int. J. Cancer, 92, 527–536.

  • van Hengel J, Gohon L, Bruyneel E, Vermeulen S, Cornelissen M, Mareel M and van Roy F . (1997). J. Cell Biol., 137, 1103–1116.

  • Van Hoorde L, Van Aken E and Mareel M . (2000). Prog. Mol. Subcell. Biol., 25, 105–134.

  • Vasioukhin V, Bauer C, Degenstein L, Wise B and Fuchs E . (2001). Cell, 104, 605–617.

  • Vermeulen SJ, Bruyneel EA, Bracke ME, De Bruyne GK, Vennekens KM, Vleminckx KL, Berx GJ, van Roy FM and Mareel MM . (1995). Cancer Res., 55, 4722–4728.

  • Vermeulen SJ, Nollet F, Teugels E, Vennekens KM, Malfait F, Philippe J, Speleman F, Bracke ME, van Roy FM and Mareel MM . (1999). Oncogene, 18, 905–915.

  • Vleminckx K, Vakaet Jr L, Mareel M, Fiers W and van Roy F . (1991). Cell, 66, 107–119.

Download references

Acknowledgements

This work was supported by the Association de la Recherche contre le Cancer (France), the Société de Secours des Amis des Sciences (France), the Fortis-Bank/Verzekeringen and the Fund for Scientific Research (FWO-Vlaanderen), Brussels, Belgium.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marc Bracke.

Rights and permissions

Reprints and permissions

About this article

Cite this article

André, F., Janssens, B., Bruyneel, E. et al. Alpha-catenin is required for IGF-I-induced cellular migration but not invasion in human colonic cancer cells. Oncogene 23, 1177–1186 (2004). https://doi.org/10.1038/sj.onc.1207238

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207238

Keywords

This article is cited by

Search

Quick links