A role for Kaiso–p120ctn complexes in cancer?

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Abstract
Kaiso is a bi-modal transcriptional repressor of the broad-complex, tramtrack and bric-a-brac/poxvirus and zinc finger (BTB/POZ) subfamily of zinc finger proteins (POZ-ZF). It binds two types of DNA sequences that are located within gene-regulatory regions — methylated CpG islands, and sequence-specific sites. A number of direct gene targets have been identified for each type of DNA interaction, and Kaiso recruits co-repressor components in both contexts. Kaiso's relevance to cancer progression has yet to be fully established, but is indicated by several factors. These include the known importance of DNA methylation in the inactivation of tumour-suppressor genes, Kaiso's direct functional links to gene targets of the canonical Wnt–β-catenin signalling pathway, and alterations in Kaiso's intracellular localization in response to normal or pathological microenvironments. Kaiso was first discovered in association with the armadillo protein p120 catenin (p120ctn), which seems to relieve sequence-specific gene repression by dissociating Kaiso from DNA. This is partially analogous to the extensively studied relief of T-cell factor (TCF)/lymphoid enhancer-binding protein (LEF) transcriptional repression by β-catenin in response to canonical Wnt signals. However, in the context of TCF/LEF, relief from transcriptional repression does not involve dissociation from the DNA. Future work needs to address whether p120ctn also modulates the repressive function of Kaiso in the context of methylated DNA and whether, within gene-regulatory regions, a functional relationship exists between the sequence-specific and methylated CpG island-binding sites of Kaiso. The identification of the signalling pathways that direct the nuclear functions of p120ctn and Kaiso is also of interest. In particular, p120ctn's known interactions with the cadherin cell–cell adhesion complex, including its associated kinases and phosphatases, with the Rho-family GTPases and with several cytoskeletal components are discussed.