title: Functional and molecular characterization of the epithelioid to round transition in human colorectal cancer LoVo cells.
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.
authors.affiliation: Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, B-9000 Ghent, Belgium.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Debruyne
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Vermeulen
authors.forename: Geert
authors.initials: G
authors.lastname: Berx
authors.forename: Marc
authors.initials: M
authors.lastname: Pocard
authors.forename: Ana-Sofia
authors.initials: AS
authors.lastname: Correia da Rocha
authors.forename: Xuedong
authors.initials: X
authors.lastname: Li
authors.forename: Luis
authors.initials: L
authors.lastname: Cirnes
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Poupon
authors.forename: Frans M
authors.initials: FM
authors.lastname: van Roy
authors.forename: Marc M
authors.initials: MM
authors.lastname: Mareel
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives* / Q000633:toxicity; D002449:Cell Aggregation / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods; D002465:Cell Movement / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine