RESUMO
Kaiso belongs to the zinc finger and broad-complex, tramtrack and bric-a-brac/poxvirus and zinc finger (BTB/POZ) protein family that has been implicated in tumorigenesis. Kaiso was first discovered in a complex with the armadillo-domain protein p120ctn and later shown to function as a transcriptional repressor. As p120ctn seems to relieve Kaiso-mediated repression, its altered intracellular localization in some cancer cells might result in aberrant Kaiso nuclear activity. Intriguingly, Kaiso's target genes include both methylated and sequence-specific recognition sites. The latter include genes that are modulated by the canonical Wnt (beta-catenin-T-cell factor) signalling pathway. Further interest in Kaiso stems from findings that its cytoplasmic versus nuclear localization is modulated by complex cues from the microenvironment.
Assuntos
Neoplasias/genética , Fatores de Transcrição/genética , Animais , Proteínas do Domínio Armadillo/genética , Cateninas , Moléculas de Adesão Celular , Proteínas do Citoesqueleto/genética , Humanos , Fosfoproteínas , Proteínas Repressoras/genética , Xenopus , Proteínas de Xenopus/genética , beta Catenina/genética , delta CateninaRESUMO
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.
