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Author(s): Jung Hwa Kim [1, 6]; Bogyou Kim [1, 6]; Ling Cai [2, 6]; Hee June Choi [1]; Kenneth A. Ohgi [2]; Chris Tran [3]; Charlie Chen [3]; Chin Ha [...]

Defining the molecular strategies that integrate diverse signalling pathways in the expression of specific gene programmes that are critical in homeostasis and disease remains a central issue in biology. This is particularly pertinent in cancer biology because downregulation of tumour metastasis suppressor genes is a common occurrence, and the underlying molecular mechanisms are not well established. Here we report that the downregulation of a metastasis suppressor gene, KAI1, in prostate cancer cells involves the inhibitory actions ofß-catenin, along with a reptin chromatin remodelling complex. This inhibitory function ofß-catenin-reptin requires both increasedß-catenin expression and recruitment of histone deacetylase activity. The coordinated actions ofß-catenin-reptin components that mediate the repressive state serve to antagonize a Tip60 coactivator complex that is required for activation; the balance of these opposing complexes controls the expression of KAI1 and metastatic potential. The molecular mechanisms underlying the antagonistic regulation ofß-catenin-reptin and the Tip60 coactivator complexes for the metastasis suppressor gene, KAI1, are likely to be prototypic of a selective downregulation strategy for many genes, including a subset of NF-?B target genes. [ABSTRACT FROM AUTHOR]