Ectopic expression of Tbx3 has suggested that this protein has the ability to increase the invasiveness of melanoma cell lines.43 In this study, we provide evidence that two small motifs contribute to transcriptional repression and serve as the interacting sites for HDAC5 in the suppression of cell invasion/migration and metastasis via the deregulation of E-cadherin expression. The gene discussed is TBX3; the disease is melanoma.