MTA2 is a member of metastasis associated family, which is highly expressed in several solid tumors and associated with tumor cells migration and invasion. Here, we report that MTA2 is acetylated at 1052 and histone acetyltransferase p300 binds to and acetylates MTA2. Furthermore, mutation of the MTA2 acetylation site inhibits the growth of colorectal cancer cells and migration and invasion of Rat1 fibroblasts. These results reveal a novel post-translational regulation of MTA2 by the way of p300-dependent acetylation, which is important for tumor cells growth and migration and provides a potential target for clinical cancer research. (C) 2014 Elsevier Inc. All rights reserved.