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

Philip R. Debruyne, Stefan J. Vermeulen, Geert Berx, Marc Pocard, Ana Sofia Correia Da Rocha, Xuedong Li, Luis Cirnes, Marie France Poupon, Frans M. Van Roy, Marc M. Mareel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)7199-7208
Number of pages10
JournalOncogene
Volume22
Issue number46
DOIs
Publication statusPublished - 16 Oct 2003
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Keywords

  • Colorectal cancer
  • E-cadherin/catenin complex
  • Invasion
  • Morphotype

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