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The αE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells

Oncogene volume 18, pages 905–915 (1999)Cite this article

Abstract

The acquisition of invasiveness is a crucial step in the malignant progression of cancer. In cancers of the colon and of other organs the E-cadherin/catenin complex, which is implicated in homotypic cell-cell adhesion as well as in signal transduction, serves as a powerful inhibitor of invasion. We show here that one allele of the αE-catenin (CTNNA1) gene is mutated in the human colon cancer cell family HCT-8, which is identical to HCT-15, DLD-1 and HRT-18. Genetic instability, due to mutations in the HMSH6 (also called GTBP) mismatch repair gene, results in the spontaneous occurrence of invasive variants, all carrying either a mutation or exon skipping in the second αE-catenin allele. The αE-catenin gene is therefore, an invasion-suppressor gene in accordance with the two-hit model of Knudsen for tumour-suppressor genes.

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References

  • Behrens J, Mareel MM, Van Roy FM and Birchmeier W. . 1989 J. Cell Biol. 108: 2435–2447.

  • Berx G, Cleton-Jansen A-M, Nollet F, de Leeuw WJF and van de Vijver MJ, Co.. 1995 EMBO J. 14: 6107–6115.

  • Bhattacharyya NP, Skandalis A, Ganesh A, Groden J and Meuth M. . 1994 Proc. Natl. Acad. Sci. USA 91: 6319–6323.

  • Bhattacharyya NP, Ganesh A, Phear G, Richards B, Skandalis A and Meuth M. . 1995 Hum. Mol. Genet. 4: 2057–2064.

  • Bracke ME, Van Larebeke NA, Vyncke BM and Mareel MM. . 1991 Br. J. Cancer 63: 867–872.

  • 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.

  • Bracke ME, Van Roy FM and Mareel MM. . 1996 In: Günthert U and Birchmeier W (eds). Attempts to Understand Metastasis Formation I. Springer: Berlin pp. 123–161.

    Book  Google Scholar 

  • Breen E, Clarke A, Steele Jr G and Mercurio AM. . 1993 Cell Adhesion Commun. 1: 239–250.

  • Bussemakers MJG, van Bokhoven A, Dikhoff X, Jansen CFJ and Schalken JA. . 1996 Clin. Exp. Metastasis 14: (Suppl. 1): 15.

  • Capizzi RL and Jameson JW. . 1973 Mutat. Res. 17: 147–148.

  • Casares S, Ionov Y, Ge H-Y, Stanbridge S and Perucho M. . 1995 Oncogene 11: 2303–2310.

  • Chen TR, Dorotinsky CS, McGuire LJ, Macy ML and Hay RJ. . 1995 Cancer Genet. Cytogenet. 81: 103–108.

  • da Costa LT, Liu B, El-Deiry WS, Hamilton SR, Kinzler KW, Vogelstein B, Markowitz S, Willson JKV, de la Chapelle A, Downey KM and So AG. . 1995 Nat. Genet. 9: 10–11.

  • Eshleman JR, Markowitz SD, Donover PS, Lang EZ, Lutterbaugh JD, Li G-M, Longley M, Modrich P, Veigl ML and Sedwick WD. . 1996 Oncogene 12: 1425–1432.

  • Ewing CM, Ru N, Morton RA, Robinson JC, Wheelock MJ, Johnson KR, Barrett JC and Isaacs WB. . 1995 Cancer Res. 55: 4813–4817.

  • Frei JV. . 1992 Cancer 69: 1108–1111.

  • Hirano S, Kimoto N, Shimoyama Y, Hirohashi S and Takeichi M. . 1992 Cell 70: 293–301.

  • Kemler R. . 1993 TIG 9: 317–321.

  • Kinzler KW and Vogelstein B. . 1996 Cell 87: 159–170.

  • Knudson AG Jr. . 1985 Cancer Res. 45: 1437–1443.

  • Koi M, Umar A, Chauhan DP, Cherian SP, Carethers JM, Kunkel TA and Boland CR. . 1994 Cancer Res. 54: 4308–4312.

  • Kouri M, Laasonen A, Mecklin J-P, Järvinen H, Franssila K and Pyrhönen S. . 1990 Cancer 65: 1825–1829.

  • Lazar V, Grandjouan S, Bognel C, Couturier D, Rougier P, Bellet D and Bressac-de Paillerets B. . 1994 Hum. Mol. Genet. 3: 2257–2260.

  • Luria SE and Delbrück M. . 1943 Genetics 28: 491–511.

  • Lynch HT and Smyrk T. . 1996 Cancer 78: 1149–1167.

  • Mareel MM, De Baetselier P and Van Roy FM. . 1991 Mechanisms of Invasion and Metastasis. CRC Press, Boca Raton, Ann Arbor, Boston. ISBN 0-8493-6254-7.

    Google Scholar 

  • Mareel M, Berx G, Van Roy F and Bracke M. . 1996 J. Cell. Biochem. 61: 524–530.

  • Mareel M, Leroy A and Bracke M. . 1997 Handbook of Clinical Neurology, Neuro-Oncology, Part III. Vinken PJ and Bruyn GW (eds).. Elsevier Vol. 25 (69): pp. 105–122.

    Google Scholar 

  • Markowitz S, Wang J, Myeroff L, Parsons R, Sun L-Z, Lutterbaugh J, Fan RS, Zborowska E, Kinzler KW, Vogelstein B, Brattain M and Wilson JKV. . 1995 Science 268: 1336–1338.

  • Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B and Kinzler KW. . 1997 Science 275: 1787–1790.

  • Morton RA, Ewing CM, Nagafuchi A, Tsukita S and Isaacs WB. . 1993 Cancer Res. 53: 3585–3590.

  • Nollet F, Van Hengel J, Berx G, Molemans F and Van Roy F. . 1995 Genomics 26: 410–413.

  • Oda T, Kanai Y, Shimoyama Y, Nagafuchi A, Tsukita S and Hirohashi S. . 1993 Biochem. Biophys. Res. Commun. 193: 897–904.

  • Papadopoulos N, Nicolaides NC, Liu B, Parsons R, Lengauer C, Palombo F, D'Arrigo A, Markowitz S, Willson JKV, Kinzler KW, Jiricny J and Vogelstein B. . 1995 Science 268: 1915–1917.

  • Parsons R, Myeroff LL, Liu B, Willson JKV, Markowitz SD, Kinzler KW and Vogelstein B. . 1995 Cancer Res. 55: 5548–5550.

  • Rhyu MS. . 1996 J. Natl. Cancer Inst. 88: 240–251.

  • Roest PAM, Roberts RG, Sugino S, van Ommen G-JB and den Dunnen JT. . 1993 Hum. Mol. Genet. 2: 1719–1721.

  • Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E and Polakis P. . 1997 Science 275: 1790–1792.

  • Shibata D, Peinado MA, Ionov Y, Malkhosyan S and Perucho M. . 1994 Nat. Genet. 6: 273–281.

  • Shimoyama Y, Nagafuchi A, Fujita S, Gotoh M, Takeichi M, Tsukita S and Hirohashi S. . 1992 Cancer Res. 52: 5770–5774.

  • Shiozaki H, Iihara K, Oka H, Kadowaki T, Matsui S, Gofuku J, Inoue M, Nagafuchi A, Tsukita S and Mori T. . 1994 Am. J. Pathol. 144: 667–674.

  • Shiozaki H, Kadowaki T, Doki Y, Inoue M, Tamura S, Oka H, Iwazawa T, Matsui S, Shimaya K, Takeichi M and Mori T. . 1995 Br. J. Cancer 71: 250–258.

  • Souza RF, Appel R, Yin J, Wang S, Smolinski KN, Abraham JM, Zou T-T, Shi Y-Q, Lei J, Cottrell J, Cymes K, Biden K, Simms L, Leggert B, Lynch PM, Frazier M, Powell SM, Harpaz N, Sugimura H, Young J and Meltzler SJ. . 1996 Nature Genetics 14: 255–257.

  • Speleman F, Colpaert C, Goovaerts G, Leroy JG and Van Marck E. . 1992 Cancer Genet. Cytogenet. 58: 176–179.

  • Takeichi M. . 1991 Science 251: 1451–1455.

  • Tompkins WAF, Watrach AM, Schmale JD, Schultz RM and Harris JA. . 1974 J. Natl. Cancer Inst. 52: 1101–1110.

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

  • Vermeulen SJ, Bruyneel EA, Van Roy FM, Mareel MM and Bracke ME. . 1995b Br. J. Cancer 72: 1447–1453.

  • Vermeulen SJ, Chen TR, Speleman F, Nollet F, Van Roy FM and Mareel MM. . 1998 Cancer Genet. Cytogenet. (in press).

  • Vermeulen S, Van Marck V, Van Hoorde L, Van Roy F, Bracke M and Mareel M. . 1996 Pathol. Res. Pract. 192: 694–707.

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

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Acknowledgements

We thank L Baeke, R Colman, A Verspeelt, K Staes and R Coquyt for technical assistance and J Roels for preparation of the illustrations. This work was supported by the Fund for Scientific Research-Flanders, The Sportvereniging tegen Kanker, The Belgian Cancer Association, The ASLK/VIVA-verzekeringen and the GOA from the Vlaamse Gemeenschap, Brussels, Belgium. FN is a Research Assistant and FVR a Research Director with the Fund for Scientific Research-Flanders.

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Authors and Affiliations

  1. Department of Radiotherapy and Nuclear Medicine, Laboratory of Experimental Cancerology, University Hospital Gent, De Pintelaan 185, Gent, B-9000, Belgium

    Stefan J Vermeulen, Krist'l M Vennekens, Fransiska Malfait, Marc E Bracke & Marc M Mareel

  2. Department of Molecular Biology, Laboratory of Molecular Cell Biology, University of Gent and VIB, Ledeganckstraat 35, Gent, B-9000, Belgium

    Friedel Nollet & Frans M van Roy

  3. Laboratory of Medical Oncology, University Hospital Brussels, Laarbeeklaan 101, Jette, B-1010, Belgium

    Erik Teugels

  4. Department of Clinical Chemistry, Microbiology and Immunology, University Hospital Gent, De Pintelaan 185, Gent, B-9000, Belgium

    Jan Philippé

  5. Department of Medical Genetics, University Hospital Gent, De Pintelaan 185, Gent, B-9000, Belgium

    Frank Speleman

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Vermeulen, S., Nollet, F., Teugels, E. et al. The αE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells. Oncogene 18, 905–915 (1999). https://doi.org/10.1038/sj.onc.1202348

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