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Functional and molecular characterization of the epithelioid to round transition in human colorectal cancer LoVo cells

Oncogene volume 22, pages 7199–7208 (2003)Cite this article

Abstract

In subclones of the human colon cancer LoVo cell line, there is a reproducible spontaneous transition from an epithelioid (E) to a round (R) morphotype. The E to R transition is associated with increased cell growth, absence of E-cadherin-dependent compaction in a slow aggregation assay, loss of contact inhibition of motility and directional migration in a wound filling motility assay. Furthermore, none of the E subclones from LoVo was invasive into chick heart fragments. This is in contrast to the R subclones that were either nonadherent or adherent and invasive. Macroarray analysis demonstrated transcriptional downregulation of plakoglobin in R type LoVo cells and this was confirmed at the level of the mRNA by quantitative RT–PCR. Western blotting showed lower expression of all components of the E-cadherin/catenin complex in R subclones. Interestingly, treatment of R subclones with the demethylating agent 5-aza-2′-deoxycytidine resulted in restoration of the E morphotype, higher expression of E-cadherin, but not plakoglobin mRNA, and higher expression of E-cadherin and plakoglobin at the protein level.

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Acknowledgements

We thank L Baeke, R Colman, G De Smet, G De Bruyne, J Roels van Kerckvoorde and A Verspeelt for technical assistance. This work was supported by the Fund for Scientific Research-Flanders (FWO, Brussels, Belgium), the ‘Sportvereniging tegen Kanker’ (Brussels, Belgium), the ‘ASLK/VIVA-verzekeringen’ (Brussels, Belgium) and the ‘G.O.A. from the Vlaamse Gemeenschap’ (Brussels, Belgium). Ph Debruyne was supported by a ‘Bijzonder Onderzoeksfonds Universiteit Gent’ (Ghent, Belgium) pre-doctoral fellowship.

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  1. Philip R Debruyne

    Present address: Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA, 19107, USA

Authors and Affiliations

  1. Department of Radiotherapy and Nuclear Medicine, Laboratory of Experimental Cancerology, Ghent University Hospital, Ghent, B-9000, Belgium

    Philip R Debruyne, Stefan J Vermeulen, Xuedong Li & Marc M Mareel

  2. Department of Molecular Biology, Molecular Cell Biology Unit, VIB-University of Ghent, Ghent, B-9000, Belgium

    Geert Berx & Frans M van Roy

  3. UMR 147 CNRS Cytogénétique Moléculaire et Oncologie, Section de Recherche, Institut Curie,  Paris, 75231, Cedex 05, France

    Marc Pocard & Marie-France Poupon

  4. Institute of Molecular Pathology and Immunology, University of Porto, Porto, 4200, Portugal

    Ana-Sofia Correia da Rocha & Luis Cirnes

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Correspondence to Marc M Mareel.

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Debruyne, P., Vermeulen, S., Berx, G. et al. Functional and molecular characterization of the epithelioid to round transition in human colorectal cancer LoVo cells. Oncogene 22, 7199–7208 (2003). https://doi.org/10.1038/sj.onc.1206628

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