Metastasis is the ultimate cause of death for most cancer patients. While many mechanisms have been delineated for regulation of growth and tumor initiation of the primary tumor, very little is known about the process of metastasis. Metastasis requires dynamic alteration of cellular processes in order for cells to disseminate from the primary tumor to distant sites. These alterations often involve dramatic changes in the regulation of cytoskeletal and cell-environment interactions. Furthermore, controlled refinement of these interactions requires feedback to regulatory networks in the nucleus. MTA2 is a member of the metastasis tumor-associated family of transcriptional regulators and is a central component of the nucleosome remodeling and histone deacetylation complex. MTA2 acts as a central hub for cytoskeletal organization and transcription and provides a link between nuclear and cytoskeletal organization. We will focus on MTA2 in this chapter, especially its role in breast cancer metastasis.